ORCID Profile
0000-0002-0035-6141
Current Organisations
University of Queensland
,
QIMR Berghofer Medical Research Institute
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Gene Expression | Genetics | Parasitology
Publisher: Springer Science and Business Media LLC
Date: 08-09-2013
DOI: 10.1038/NG.2757
Abstract: Cystic echinococcosis (hydatid disease), caused by the tapeworm E. granulosus, is responsible for considerable human morbidity and mortality. This cosmopolitan disease is difficult to diagnose, treat and control. We present a draft genomic sequence for the worm comprising 151.6 Mb encoding 11,325 genes. Comparisons with the genome sequences from other taxa show that E. granulosus has acquired a spectrum of genes, including the EgAgB family, whose products are secreted by the parasite to interact and redirect host immune responses. We also find that genes in bile salt pathways may control the bidirectional development of E. granulosus, and sequence differences in the calcium channel subunit EgCavβ1 may be associated with praziquantel sensitivity. Our study offers insights into host interaction, nutrient acquisition, strobilization, reproduction, immune evasion and maturation in the parasite and provides a platform to facilitate the development of new, effective treatments and interventions for echinococcosis control.
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.IJPARA.2012.06.002
Abstract: Insulin receptors have been previously identified in Schistosoma japonicum that can bind human insulin. We used the purified recombined protein of the ligand domain of S.japonicum insulin receptor 2 (SjLD2) in three independent murine vaccine/challenge trials. Compared with controls, vaccination of mice with SjLD2 resulted in a significant reduction in faecal eggs, the stunting of adult worms and a reduction in liver granuloma density in all three trials. Furthermore, in the final trial, in which mature intestinal eggs were also quantified, there was a reduction in their number. These results suggest that development of a vaccine based on rSjLD2 for preventing transmission of zoonotic schistosomiasis is feasible.
Publisher: Biology Centre, AS CR
Date: 06-2001
DOI: 10.14411/FP.2001.028
Publisher: Frontiers Media SA
Date: 05-03-2021
DOI: 10.3389/FIMMU.2021.599014
Abstract: Schistosomes infect about 250 million people globally causing the devastating and persistent disease of schistosomiasis. These blood flukes have a complicated life cycle involving alternating infection of freshwater snail intermediate and definitive mammalian hosts. To survive and flourish in these erse environments, schistosomes transition through a number of distinct life-cycle stages as a result of which they change their body plan in order to quickly adapt to each new environment. Current research suggests that stem cells, present in adults and larvae, are key in aiding schistosomes to facilitate these changes. Given the recent advances in our understanding of schistosome stem cell biology, we review the key roles that two major classes of cells play in the different life cycle stages during intramolluscan and intramammalian development these include the germinal cells of sporocysts involved in asexual reproduction in molluscan hosts and the neoblasts of adult worms involved in sexual reproduction in human and other mammalian hosts. These studies shed considerable new light in revealing the stem cell heterogeneity driving the propagation of the schistosome life cycle. We also consider the possibility and value of establishing stem cell lines in schistosomes to advance schistosomiasis research. The availability of such self-renewable resources will provide new platforms to study stem cell behavior and regulation, and to address fundamental aspects of schistosome biology, reproductive development and survival. In turn, such studies will create new avenues to unravel in idual gene function and to optimize genome-editing processes in blood flukes, which may lead to the design of novel intervention strategies for schistosomiasis.
Publisher: Public Library of Science (PLoS)
Date: 03-10-2011
Publisher: Oxford University Press (OUP)
Date: 02-04-2007
DOI: 10.1111/J.1365-2249.2007.03386.X
Abstract: An Echinococcus granulosus cDNA sequence coding for EpC1, a proven serodiagnostic marker for cystic echinococcosis (CE, hydatid disease), has high amino acid sequence identity to a paralogue from Taenia solium, the cause of neurocysticercosis (NCC). To determine diagnostic antibody-binding regions on EpC1 recognized specifically by CE sera, 10 truncated regions (P1–10) of the immunogenic protein were expressed in Escherichia coli and subjected to immunoblotting. One peptide, designated peptide 5 [P5, fused with glutathione-S-transferase (GST)] was positively recognized by sera from mice experimentally infected with oncospheres of E. granulosus and sera from surgically confirmed CE patients. Sera from NCC patients did not react with any of the peptides used. There are four amino acid substitutions in P5 compared with the T. solium sequence and these may form part of the epitope inducing CE-specific antibody. Ninety-seven per cent (58 of 60) of sera from confirmed CE patients recognized P5-GST, which was higher than the parent EpC1 fused with GST which reacted with 92% (55 of 60) of the sera. A population screening survey showed that 424 human sera collected from communities in Xinjiang, an area in China endemic for CE, exhibited 4·5% and 3·3% positivity in immunoblotting analysis to EpC1 and P5, respectively 19·8% of these sera reacted positively against hydatid cyst fluid (HCF) antigen B. Low numbers of surgical CE cases have been reported from this population, suggesting that HCF-based serology lacks specificity and that EpC1 or its contained P5 peptide may prove more accurate for seroepidemiological surveys of CE.
Publisher: Elsevier BV
Date: 1996
DOI: 10.1016/0166-0934(95)01916-2
Abstract: Ultra-cryomicrotomy and electron microscopy were used to investigate membranous structures in dengue virus-infected mammalian and insect cells. The cryo-sectioned s les displayed ultrastructure comparable to their resin-embedded counterparts with all previously identified virus-induced structures being observed. Structures not previously identified were also found. In particular, membrane-bound packets of vesicles, 100-200 nm in diameter were seen distributed throughout areas of virus-induced membrane proliferation. These packets were clearly distinct from virion arrays. Small smooth membrane vesicles, previously found to contain thread-like enclosures (M.L. Ng, J. Gen. Virol. 68 (1987) 577-582), were frequently observed to contain dense staining material, however the exact nature of this material remains unclear. Virus-induced modification of golgi-like and/or ER membranes was also observed and may represent early events in the generation of the smooth membrane vesicles seen during infection. We suggest that cryosectioning is the method of choice to investigate membrane rearrangement induced by this family of viruses and that a diamond knife and modified staining techniques, as utilised in this report, be employed to enhance morphology and section preservation.
Publisher: Public Library of Science (PLoS)
Date: 26-12-2007
Publisher: Wiley
Date: 08-2000
DOI: 10.1046/J.1365-3024.2000.00319.X
Abstract: The 22.6 kDa tegumental-associated antigens of Schistosoma mansoni (Sm22.6) and Schistosoma japonicum (Sj22.6) are of recognized interest in schistosomiasis vaccine development, although no direct vaccination/challenge experiments using either Sm22.6 or Sj22.6 had been previously described. We report that Escherichia coli-expressed reSj22.6 failed to protect mice or water buffaloes against subsequent challenge with S. japonicum cercariae. This was despite the fact that specific IgG (buffaloes) and IgG and IgE (CBA mice) antibodies were generated against the 22.6 kDa molecule, observations consistent with some of our earlier findings. We could find no evidence from immunolocalization studies that Sj22.6 is expressed or exposed on the surface of the adult parasite since it appears to be restricted to the apical cytoplasm of the tegument and is not associated with the apical or basal membrane or any membrane-bound structures in the apical cytoplasm. Nevertheless, Sj22.6 must be released to the immune system during the course of infection because specific anti-Sj22.6 IgG antibodies were present in the sera of nonvaccinated but challenged mice. We conclude that it may be necessary to produce reSj22.6 in a more relevant expression system, such as baculovirus, to further establish its vaccine potential and that detailed immunochemical and immunolocalization studies of early developmental stages may be necessary to determine how Sj22.6 is released or shed in S. japonicum infections.
Publisher: Elsevier BV
Date: 09-1998
DOI: 10.1016/S0020-7519(98)00114-3
Abstract: Eight lectin probes were used to detect a range of carbohydrate residues in the tegument matrix of Schistosoma japonicum. In addition, other areas of the parasite, such as the gut, vitelline glands and flame cells, were examined for carbohydrate residues. Some minor differences in the carbohydrate residue composition between tegument orientations and between the sexes were identified. Differences between the distribution of carbohydrate residues of S. japonicum examined in this study and previous reports of Schistosoma mansoni were also noted. This study further illustrates the high level of complexity within the tegument of the adult S. japonicum and has demonstrated differences between this species and the widely studied S. mansoni.
Publisher: CSIRO Publishing
Date: 2013
DOI: 10.1071/HR13007
Abstract: John Frederick Adrian Sprent was the outstanding figure in Parasitology in Australia in the twentieth century. He established and held the Chair of the Department of Parasitology at the University of Queensland from 1956 to 1983. He was internationally recognized by parasitologists, both for his work on ascaridoid nematodes and for his huge contribution as Editor-in-Chief of the International Journal for Parasitology from 1974 to 1993.
Publisher: Diva Enterprises Private Limited
Date: 2018
Publisher: Public Library of Science (PLoS)
Date: 16-05-2013
Publisher: Public Library of Science (PLoS)
Date: 22-05-2015
Publisher: Elsevier BV
Date: 06-2009
DOI: 10.1016/J.MOLBIOPARA.2009.01.009
Abstract: Members of the leucine-rich repeat protein family are involved in erse functions including protein phosphatase 2-inhibition, cell cycle regulation, gene regulation and signalling pathways. A novel Schistosoma mansoni gene, called SmLANP, presenting homology to various genes coding for proteins that belong to the super family of leucine-rich repeat proteins, was characterized here. SmLANP was 1184bp in length as determined from cDNA and genomic sequences and encoded a 296 amino acid open reading frame that spanning from 6 to 894bp. The predicted amino acid sequence had a calculated molecular weight of 32kDa. Analysis of the predicted sequence indicated the presence of 3 leucine-rich domains (LRR) located in the N-terminal region and an aspartic acid rich region in the C-terminal end. SmLANP transcript is expressed in all stages of the S. mansoni life cycle analyzed, exhibiting the highest expression level in males. The SmLANP protein was expressed in a GST expression system and antibodies raised in mice against the recombinant protein. By immunolocalization assay, using adult worms, it was shown that the protein is mainly present in the cell nucleus through the whole body and strongly expressed along the tegument cell body nuclei of adult worms. As members of this family are usually involved in protein-protein interaction, a yeast two hybrid assay was conducted to identify putative binding partners for SmLANP. Thirty-six possible partners were identified, and a protein ATP synthase subunit alpha was confirmed by pull down assays, as a binding partner of the SmLANP protein.
Publisher: Elsevier BV
Date: 12-2007
Publisher: Cambridge University Press (CUP)
Date: 1997
DOI: 10.1017/S0031182096008001
Abstract: This paper describes the localization of paramyosin immunoreactivity in Schistosoma japonicum and represents the first comparative immunolocalization study among schistosome adult, cercariae and lung schistosomula by electron microscopy. A polyclonal antibody was utilized to immunolabel paramyosin or paramyosin-like proteins. Paramyosin was localized within the muscle layer of all 3 developmental stages. Furthermore, paramyosin was localized within granules of the post-acetabular glands of cercariae, and within the tegument matrix and surface of lung schistosomules. Adults and cercariae did not display any detectable paramyosin on the surface or within the tegument. The possible functions of paramyosin within S. japonicum and the relevance of these findings in relation to the reported protective properties of paramyosin as an anti-schistosome vaccine target molecule are discussed.
Publisher: Elsevier BV
Date: 06-1998
Abstract: In a previous study on the replication of Kunjin virus using immunoelectron microscopy (E. G. Westaway, J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A. Khromykh, 1997, J. Virol. 71, 6650-6661), NS1 and NS3 were found associated with double-stranded RNA (dsRNA) within vesicle packets (VP) in infected Vero cells, suggesting that these induced membrane structures may be the cytoplasmic sites of RNA replication. NS2B and NS3 (comprising the virus-encoded protease) were colocalized within distinct paracrystalline (PC) or convoluted membranes (CM), also induced in the cytoplasm, suggesting that these membranes are the sites of proteolytic cleavage. In this study we found by immunofluorescence (IF) that the small hydrophobic nonstructural proteins NS2A and NS4A were located in discrete foci in the cytoplasm of infected cells at both 16 and 24 h postinfection, partially coincident with dsRNA foci. In cryosections of infected cells at 24 h, NS2A was located by immunogold labeling primarily within VP, associated with labeled dsRNA. NS2A fused to glutathione S-transferase (GST) bound strongly to the 3' untranslated region of Kunjin RNA and also to the proposed replicase components NS3 and NS5 in cell lysates. NS4A was localized by immunogold labeling within a majority of the virus-induced membranes, including VP, CM, and PC. GST-NS4A bound weakly to the 3' untranslated region of Kunjin RNA but was bound to NS4A strongly and to most of the other viral nonstructural proteins, including NS3 and NS5. Taken together the results indicate that the flavivirus replication complex includes NS2A and NS4A in the VP in addition to the previously identified NS1 and NS3.
Publisher: Elsevier BV
Date: 05-2006
DOI: 10.1016/J.IJPARA.2006.01.015
Abstract: The gastrointestinal tracts of multi-cellular blood-feeding parasites are targets for vaccines and drugs. Recently, recombinant vaccines that interrupt the digestion of blood in the hookworm gut have shown efficacy, so we explored the intestinal transcriptomes of the human and canine hookworms, Necator americanus and Ancylostoma caninum, respectively. We used Laser Microdissection Microscopy to dissect gut tissue from the parasites, extracted the RNA and generated cDNA libraries. A total of 480 expressed sequence tags were sequenced from each library and assembled into contigs, accounting for 268 N. americanus genes and 276 A. caninum genes. Only 17% of N. americanus and 36% of A. caninum contigs were assigned Gene Ontology classifications. Twenty-six (9.8%) N. americanus and 18 (6.5%) A. caninum contigs did not have homologues in any databases including dbEST-of these novel clones, seven N. americanus and three A. caninum contigs had Open Reading Frames with predicted secretory signal peptides. The most abundant transcripts corresponded to mRNAs encoding cholesterol-and fatty acid-binding proteins, C-type lectins, Activation-Associated Secretory Proteins, and proteases of different mechanistic classes, particularly astacin-like metallopeptidases. Expressed sequence tags corresponding to known and potential recombinant vaccines were identified and these included homologues of proteases, anti-clotting factors, defensins and integral membrane proteins involved in cell adhesion.
Publisher: American Society for Microbiology
Date: 04-2007
DOI: 10.1128/JB.01590-06
Abstract: Streptococcus dysgalactiae subsp. equisimilis strains (group G streptococcus [GGS]) are largely defined as commensal organisms, which are closely related to the well-defined human pathogen, the group A streptococcus (GAS). While lateral gene transfers are emerging as a common theme in these species, little is known about the mechanisms and role of these transfers and their effect on the population structure of streptococci in nature. It is now becoming evident that bacteriophages are major contributors to the genotypic ersity of GAS and, consequently, are pivotal to the GAS strain structure. Furthermore, bacteriophages are strongly associated with altering the pathogenic potential of GAS. In contrast, little is know about phages from GGS and their role in the population dynamics of GGS. In this study we report the first complete genome sequence of a GGS phage, Φ3396. Exhibiting high homology to the GAS phage Φ315.1, the chimeric nature of Φ3396 is unraveled to reveal evidence of extensive ongoing genetic ersity and dissemination of streptococcal phages in nature. Furthermore, we expand on our recent findings to identify inducible Φ3396 homologues in GAS from a region of endemicity for GAS and GGS infection. Together, these findings provide new insights into not only the population structure of GGS but also the overall population structure of the streptococcal genus and the emergence of pathogenic variants.
Publisher: WHO Press
Date: 09-2006
Abstract: To determine the true community prevalence of human cystic (CE) and alveolar (AE) echinococcosis (hydatid disease) in a highly endemic region in Ningxia Hui, China, by detecting asymptomatic cases. Using hospital records and "AE-risk" landscape patterns we selected study communities predicted to be at risk of human echinococcosis in Guyuan, Longde and Xiji counties. We conducted community surveys of 4773 in iduals from 26 villages in 2002 and 2003 using questionnaire analysis, ultrasound examination and serology. Ultrasound and serology showed a range of prevalences for AE (0-8.1% mean 2%) and CE (0-7.4% mean 1.6%), with the highest prevalence in Xiji (2% for CE, 2.5% for AE). There were significant differences in the prevalence of CE, AE and total echinococcosis between the three counties and villages (with multiple degrees of freedom). While hospital records showed 96% of echinococcosis cases attributable to CE, our survey showed a higher prevalence of human AE (56%) compared to CE (44%). Questionnaire analysis revealed that key risk factors for infection were age and dog ownership for both CE and AE, and Hui ethnicity and being female for AE. Drinking well-water decreased the risk for both AE and CE. Echinococcosis continues to be a severe public health problem in this part of China because of unhygienic practices/habits and poor knowledge among the communities regarding this disease.
Publisher: Elsevier BV
Date: 06-2021
Publisher: Baishideng Publishing Group Inc.
Date: 2005
Abstract: This paper deals with all aspects of liver alveolar echin-ococcosis (AE) including epidemiology, pathology, clinical manifestations, imaging examinations, diagnosis and differential diagnosis, surgical treatment and chemotherapy. The review is not only based on personal clinical experiences but also in combination with relative basic research such as proliferation and growth of alveococcus, preclinical studies of a novel compound extracted from TCM for treatment of liver AE, and molecular immunology used for specific AE diagnosis, etc.
Publisher: Elsevier BV
Date: 09-2013
DOI: 10.1016/J.IJPARA.2013.04.003
Abstract: The tegument, or body wall, of schistosomes is the primary tissue for host interaction and site targeted schistosome vaccination. However, many aspects of the cell biology, particularly differentiation and maintenance, remain uncharacterised. A leading vaccine candidate, Schistosoma mansoni tetraspanin 2 has proven efficacy in experimental models, but its function, precise subcellular location in the tegument and role in tegument biology is not well understood. A primary question is whether this molecule is a true surface molecule, that is, whether it appears within the apical membrane of the tegument. Hitherto, the target sequence for antibody localisation studies had not been available for advanced subcellular localisation studies, such as immuno-electron microscopy, due to aldehyde sensitivity. To circumvent this problem, we adapted the methods of high pressure freezing and cryosubstitution with uranyl acetate for immuno-electron microscopy. The tri-dimensional structure of tegument membranes was resolved using electron tomography. Immunolocalisation of Schistosoma mansoni tetraspanin 2 demonstrates that the molecule is localised to tegument membrane compartments, but predominantly within internal structures associated with surface invaginations and internal vesicles. Surprisingly, no label was found at the virtual surface of the parasite. The significance of this localisation pattern is discussed.
Publisher: Cambridge University Press (CUP)
Date: 10-2004
DOI: 10.1017/S0031182004005773
Abstract: Surgical treatment of human hydatidsosis involves the use of various scolicidal agents to kill infective Echinococcus granulosus protoscoleces that may disseminate into the peritoneal cavity during surgery and potentially re-infect the patient. Currently, no scolicidal agent is completely effective in killing intracystic protoscoleces in humans. Cyclosporin A (CsA) has previously been found to be lethal for E. granulosus protoscoleces in vitro. In this study, we further assessed the effectiveness of CsA as a scolicidal agent by testing the toxic effect of CsA at higher doses over various time-periods. Experiments were performed on activated and unactivated protoscoleces cultured in nutrient medium or sheep hydatid cyst fluid. All activated protoscoleces were killed following culture in 100 microg/ml of CsA for 3 days and 50 or 20 microg/ml for 5 days. The lethal effect of CsA on unactivated protoscoleces varied but reached 100% over 15 days in culture with 100 or 50 microg/ml of CsA. Pulse treatment of protoscoleces with 50, 20 or 10 microg/ml of CsA for 5 min or 72 h killed all parasites by day 10 and day 5 respectively. Untreated protoscoleces remained greater than 95 % viable for the duration of experiments. Changes in protoscolex ultrastructure induced by treatment with 10 microg/ml of CsA over 10 days in in vitro culture was assessed by TEM. Protoscolex alterations observed in treated parasites included an increase in cellular vacuolization, swelling of mitochondria, rounding of cells, damage to the tegument, decrease in glycogen, a breakdown of the extracellular matrix and an increase in lipid globules. The untreated protoscoleces, by comparison, had few changes during the 10-day culture period with the exception of large amounts of extracellular glycogen observed in the protoscoleces at culture days 7 and 10. From these results, CsA is clearly an effective scolicidal agent in vitro that may have potential application as a new therapeutic agent in the treatment of human hydatid disease.
Publisher: Public Library of Science (PLoS)
Date: 08-03-2018
Publisher: Cambridge University Press (CUP)
Date: 23-08-2007
DOI: 10.1017/S0031182007003393
Abstract: A partial cDNA sequence was obtained from the human blood fluke, Schistosoma mansoni using a signal sequence trap approach. The full-length cDNA was cloned and termed Sm-7TM . The corresponding open reading frame had 7 membrane spanning domains and shared identity with a small, novel group of seven transmembrane (7TM) receptors from vertebrates and invertebrates, including the human ee3 receptor – a heptahelical protein implicated in neuronal signalling. Phylogenetic analysis of this novel family showed that the Sm -7TM ORF formed a clade with exclusively invertebrate sequences. Based on topology modelling with ee3, Sm -7TM was predicted to possess an intracellular C-terminal tail, which was expressed as a soluble thioredoxin fusion protein ( Sm -7TMC) in Escherichia coli and purified using metal ion-affinity chromatography. A polyclonal antiserum against this domain was used to detect Sm -7TM in detergent-soluble parasite extracts and to immunolocalize the receptor to the tegument of adult S. mansoni .
Publisher: Wiley
Date: 27-03-2007
DOI: 10.1111/J.1365-3156.2007.01834.X
Abstract: We correlated ultrasound (US) imaging classifications for human alveolar echinococcosis (AE) and cystic echinococcosis (CE) with serology (ELISA and immunoblotting (IB) incorporating native and recombinant urified echinococcal antigens) in community surveys (2001-2003) and follow-up (2002 and 2003) of US-confirmed cases in Ningxia, China. One hundred and seventy-one cases (96 with AE, 75 with CE) were identified of these, US classification and serological data were obtained for 142 and 112 cases, respectively. Seropositive-rates increased in CE patients with highly viable unilocular cyst lesions (Types CL, CE 1 or CE 2) to degenerating primary lesions (CE 3), but then decreased in subjects with inactive (CE 4) or dead (CE 5) cysts. In contrast, there was a constant increase in seropositivity from the early (P1, P2) to the advanced stages (P3, P4) with AE cases. For US-confirmed cases, follow-up by US combined with serology is invaluable for studying the clinical progression of echinococcosis and for detecting recurrent cysts or reinfection post-treatment.
Publisher: Springer Science and Business Media LLC
Date: 18-06-2006
DOI: 10.1038/NM1430
Abstract: Schistosomes are blood-dwelling flukes that infect 200 million people worldwide and are responsible for hundreds of thousands of deaths annually. Using a signal sequence trap, we cloned from Schistosoma mansoni two cDNAs, Sm-tsp-1 and Sm-tsp-2, encoding the tetraspanin (TSP) integral membrane proteins TSP-1 and TSP-2. We raised antibodies to recombinant TSP fusion proteins and showed that both proteins are exposed on the surface of S. mansoni. Recombinant TSP-2, but not TSP-1, is strongly recognized by IgG1 and IgG3 (but not IgE) from naturally resistant in iduals but is not recognized by IgG from chronically infected or unexposed in iduals. Vaccination of mice with the recombinant proteins followed by challenge infection with S. mansoni resulted in reductions of 57% and 64% (TSP-2) and 34% and 52% (TSP-1) for mean adult worm burdens and liver egg burdens, respectively, over two independent trials. Fecal egg counts were reduced by 65-69% in both test groups. TSP-2 in particular provided protection in excess of the 40% benchmark set by the World Health Organization for progression of schistosome vaccine antigens into clinical trials. When coupled with its selective recognition by naturally resistant people, TSP-2 seems to be an effective vaccine antigen against S. mansoni.
Publisher: Springer Science and Business Media LLC
Date: 02-02-2018
Publisher: Biology Centre, AS CR
Date: 03-2000
DOI: 10.14411/FP.2000.006
Abstract: The ultrastructure of the scolex tegument, bothridial pits (=ciliated pits) and rhyncheal system of Otobothrium mugilis Hiscock, 1954 is described from plerocerci collected from the teleosts Arius graeffei Kner et Steindachner and Mugil cephalus Linnaeus. Scanning electron microscopy revealed that filamentous microtriches with shortened caps are abundant across the entire surface of the tegument. Palmate microtriches are dominant on the bothridia and their margins. The surfaces of bothridial pits were covered with large bifid microtriches. The bothridial pits are strongly muscularised invaginations of the tegument. Nervous tissues were not observed within the pits and it is probable that these structures function as accessory attachment structures. The wall of each tentacle sheath consists of one to three bands of fibrils, lined internally by a thin cytoplasmic layer. The tentacular walls are cellular, containing myofilaments. The fibrils of the tentacular walls are arranged into discrete blocks of parallel fibrils and appear to be intracellular. Tentacular walls are lined externally by a modified membrane with an external glycocalyx. Tentacular hooks are solid, bound externally by a membrane. The body of the hook contains numerous longitudinal canaliculi and an electron-opaque medulla lies at the centre of the hook.
Publisher: Elsevier BV
Date: 2006
Publisher: Springer Science and Business Media LLC
Date: 2000
Abstract: Polyclithrum mugilini Rogers, 1967, a parasite of Mugil cephalus Linnaeus, is redescribed from type-material from Lake Seminole, Georgia, USA. Three new species of Polyclithrum Rogers, 1967 are also described: P. alberti n. sp. from M. cephalus from the Albert River, Queensland, Australia P. boegeri n. sp. from M. platanus Günther from Rio da Guarda, State of Rio de Janeiro, Brazil and P. corallense n. sp. from M. cephalus from Heron Island, Great Barrier Reef, Australia. The four species can be distinguished by the size and shape of haptoral sclerites, but in particular by accessory bar number 3, the dorsal bar, the marginal hooks and the hamulus point to shaft angle. The validity of Micropolyclithrum parvum Skinner, 1975, a parasite of M. cephalus in Biscayne Bay, Florida, is discussed, and a key to the species of Polyclithrum is presented.
Publisher: Wiley
Date: 2000
DOI: 10.1002/1097-4687(200012)246:3<198::AID-JMOR4>3.0.CO;2-2
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.IJPARA.2015.12.004
Abstract: For hepatic schistosomiasis the egg-induced granulomatous response and the development of extensive fibrosis are the main pathologies. We used a Schistosoma japonicum-infected mouse model to characterise the multi-cellular pathways associated with the recovery from hepatic fibrosis following clearance of the infection with the anti-schistosomal drug, praziquantel. In the recovering liver splenomegaly, granuloma density and liver fibrosis were all reduced. Inflammatory cell infiltration into the liver was evident, and the numbers of neutrophils, eosinophils and macrophages were significantly decreased. Transcriptomic analysis revealed the up-regulation of fatty acid metabolism genes and the identification of Peroxisome proliferator activated receptor alpha as the upstream regulator of liver recovery. The aryl hydrocarbon receptor signalling pathway which regulates xenobiotic metabolism was also differentially up-regulated. These findings provide a better understanding of the mechanisms associated with the regression of hepatic schistosomiasis.
Publisher: Cambridge University Press
Date: 2012
Publisher: Springer Science and Business Media LLC
Date: 10-2004
Publisher: Elsevier BV
Date: 08-2022
Publisher: Oxford University Press (OUP)
Date: 06-12-2018
Publisher: Public Library of Science (PLoS)
Date: 09-02-2727
Publisher: Public Library of Science (PLoS)
Date: 15-04-2010
Publisher: Cambridge University Press (CUP)
Date: 13-02-2020
DOI: 10.1017/S0031182020000232
Abstract: The native rat lungworm ( Angiostrongylus mackerrasae ) and the invasive rat lungworm ( Angiostrongylus cantonensis ) occur in eastern Australia. The species identity of A. mackerrasae remained unquestioned until relatively recently, when compilation of mtDNA data indicated that A. mackerrasae sensu Aghazadeh et al . (2015 b ) clusters within A. cantonensis based on their mitochondrial genomes (mtDNA). To re-evaluate the species identity of A. mackerrasae , we sought material that would be morphologically conspecific with A. mackerrasae . We combined morphological and molecular approaches to confirm or refute the specific status of A. mackerrasae . Nematodes conspecific with A. mackerrasae from Rattus fuscipes and Rattus rattus were collected in Queensland, Australia. Morphologically identified A. mackerrasae voucher specimens were characterized using lification of cox1 followed by the generation of reference complete mtDNA. The morphologically distinct A. cantonensis , A. mackerrasae and A. malaysiensis are genetically distinguishable forming a monophyletic mtDNA lineage. We conclude that A. mackerrasae sensu Aghazadeh et al . (2015 b ) is a misidentified specimen of A. cantonensis . The availability of the mtDNA genome of A. mackerrasae enables its unequivocal genetic identification and differentiation from other Angiostrongylus species.
Publisher: Elsevier BV
Date: 02-2004
DOI: 10.1016/J.GENE.2003.10.027
Abstract: A full-length cDNA sequence coding for Echinococcus granulosus thioredoxin peroxidase (EgTPx) was isolated from a sheep strain protoscolex cDNA library by immunoscreening using a pool of sera from mice infected with oncospheres. EgTPx expressed as a fusion protein with glutathione S-transferase (GST) exhibited significant thiol-dependent peroxidase activity that protected plasmid DNA from damage by metal-catalyzed oxidation (MCO) in vitro. Furthermore, the suggested antioxidant role for EgTPx was reinforced in an in vivo assay, whereby its expression in BL21 bacterial cells markedly increased the tolerance and survival of the cells to high concentrations of H2O2 compared with controls. Immunolocalization studies revealed that EgTPx was specifically expressed in all tissues of the protoscolex and brood capsules. Higher intensity of labelling was detected in many, but not all, calcareous corpuscle cells in protoscoleces. The purified recombinant EgTPx protein was used to screen sera from heavily infected mice and patients with confirmed hydatid infection. Only a portion of the sera reacted positively with the EgTPx-GST fusion protein in Western blots, suggesting that EgTPx may form antibody-antigen complexes or that responses to the EgTPx antigen may be immunologically regulated. Recombinant EgTPx may prove useful for the screening of specific inhibitors that could serve as new drugs for treatment of hydatid disease. Moreover, given that TPx from different parasitic phyla were phylogenetically distant from host TPx molecules, the development of antiparasite TPx inhibitors that do not react with host TPx might be feasible.
Publisher: Mary Ann Liebert Inc
Date: 09-2011
Abstract: Approximately one billion people are infected with hookworms and/or blood flukes (schistosomes) in developing countries. These two parasites are responsible for more disability adjusted life years lost than most other neglected tropical diseases (NTDs), and together, are second only to malaria. Although anthelmintic drugs are effective and widely available, they do not protect against reinfection, resistant parasites are likely to emerge, and mass drug administration programs are unsustainable. Therefore, there is a pressing need for the development of vaccines against these parasites. In recent years, there have been major advances in our understanding of hookworms and schistosomes at the molecular level through the use of "omics" technologies. The secretomes of these parasites have been characterized using transcriptomics, genomics, proteomics, and newly developed gene manipulation and silencing techniques, and the proteins of interest are now the target of novel antigen discovery approaches, notably immunomics. This research has resulted in the discovery, development, and early stage clinical trials of subunit vaccines against hookworms and schistosomes.
Publisher: Cambridge University Press (CUP)
Date: 03-1999
DOI: 10.1017/S0031182098003783
Abstract: Murine antibodies, raised against a purified recombinant 30 kDa laminin-binding protein from Echinococcus granulosus , were used to investigate the tissue distribution of the native protein in protoscoleces and brood capsules. Immunofluorescence, in combination with confocal microscopy, revealed that the protein was distributed in small annular foci near the peripheral regions of the protoscoleces. Immunoelectron microscopy of thawed cryosections demonstrated that the laminin-binding protein was present in the cytoplasm of tegumentary cytons and myocytons, but not in cells of the excretory system. The protein was associated with amorphous regions of the cytoplasm, and was not expressed at the surfaces of cells. This distribution resembles those of other invertebrate laminin-binding proteins, which are thought to act in the cell cycle and cell proliferation events. A low degree of label was consistently detected in extracellular matrices of the protoscolex.
Publisher: Public Library of Science (PLoS)
Date: 06-12-2012
Publisher: Oxford University Press (OUP)
Date: 17-05-2015
Publisher: Wiley
Date: 21-01-2020
DOI: 10.1111/PIM.12693
Abstract: Schistosomes infect approximately 250 million people worldwide. To date, there is no effective vaccine available for the prevention of schistosome infection in endemic regions. There remains a need to develop means to confer long-term protection of in iduals against reinfection. In this study, an annexin, namely annexin B30, which is highly expressed in the tegument of Schistosoma mansoni was selected to evaluate its immunogenicity and protective efficacy in a mouse model. Bioinformatics analysis showed that there were three potential linear B-cell epitopes and four conformational B-cell epitopes predicted from annexin B30, respectively. Full-length annexin B30 was cloned and expressed in Escherichia coli BL21(DE3). In the presence of adjuvants, the soluble recombinant protein was evaluated for its protective efficacy in two independent vaccine trials. Immunization of CBA mice with recombinant annexin B30 formulated either in alum only or alum/CpG induced a mixed Th1/Th2 cytokine profile but no significant protection against schistosome infection was detected. Recombinant annexin B30 did not confer significant protection against the parasite. The molecule may not be suitable for vaccine development. However, it could be an ideal biomarker recommended for immunodiagnostics development.
Publisher: Springer Science and Business Media LLC
Date: 02-2006
DOI: 10.1038/NM0206-170
Publisher: Springer Science and Business Media LLC
Date: 17-06-2020
Publisher: Elsevier BV
Date: 07-2005
DOI: 10.1016/J.BIOCEL.2005.01.015
Abstract: Schistosomes are pathogenic helminth parasites of human portal veins. Their body wall is a highly active syncytial tegument involved in an array of host interactions. The cytoskeletal organization and dynamics of this syncytium are poorly understood, but predominant motor components are the LC8 class of cytoplasmic dynein light chains (DLC). Four LC8 members occur in schistosomes, two of which are expressed in the tegument. Here, we describe the cytoplasmic distribution, stage-specific expression and cellular location of two erse LC8 molecules of Schistosoma japonicum. SjDLC1 was detected in surface-membrane specific extracts of adult worms and was shown by quantitative immuno-electron microscopy to predominate along heptalaminate membranes of the worm surface. SjDLC3 also occurs in the tegument, but was shown to be present in basal layers of the tegument and did not preferentially co-localize with particular membrane components. SjDLC3 was also detected in the gastrodermis. SjDLC1 is expressed only in mammalian-parasitic stages, whereas SjDLC3 is expressed throughout the life-cycle. The data suggest that SjDLC1 is preferentially located to the host-interactive distal parasite membrane, and plays a role in surface membrane dynamics, while SjDLC3 is a ubiquitous motor component of schistosome epithelia of all stages.
Publisher: MDPI AG
Date: 28-03-2019
DOI: 10.3390/IJMS20071565
Abstract: We showed previously that the Schistosoma japonicum insulin-like peptide (SjILP) binds the worm insulin receptors, thereby, activating the parasite’s insulin pathway and emphasizing its important role in regulating uptake of glucose, a nutrient essential for parasite survival. Here we show that SjILP is differentially expressed in the schistosome life cycle and is especially highly transcribed in eggs, miracidia, and adult female worms. RNA inference was employed to knockdown SjILP in adults in vitro, with suppression confirmed by significantly reduced protein production, declined adenosine diphosphate levels, and reduction in glucose consumption. Immunolocalization showed that SjILP is located to lateral gland cells of mature intra-ovular miracidia in the schistosome egg, and is distributed on the ciliated epithelium and internal cell masses of newly transformed miracidia. In schistosomula, SjILP is present on the tegument in two antero-lateral points, indicating highly polarized expression during cercarial transformation. Analysis of serum from S. japonicum-infected mice by ELISA using a recombinant form of SjILP as an antigen revealed IgG immunoreactivity to this molecule at 7 weeks post-infection indicating it is likely secreted from mature eggs into the host circulation. These findings provide further insights on ILP function in schistosomes and its essential roles in parasite survival and growth in different development stages.
Publisher: Elsevier BV
Date: 08-2004
Publisher: Elsevier BV
Date: 12-2019
DOI: 10.1016/J.MOLBIOPARA.2019.111231
Abstract: Schistosomes are parasitic blood flukes that infect approximately 250 million people worldwide. The disease known as schistosomiasis, is the second most significant tropical parasitic disease after malaria. Praziquantel is the only effective drug currently licensed for schistosomiasis and there are concerns about resistance to the drug. There has been much effort to develop vaccines against schistosomiasis to produce long-term protection in endemic regions. Surface-associated proteins, and in particular, those expressed in the body wall, or tegument, have been proposed as potential vaccine targets. Of these, annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the structural and immunobiochemical characterization of four homologous annexins namely annexin B30, annexin B5a, annexin B7a and annexin B5b from S. mansoni. Bioinformatics analysis showed that there was no signal peptide predicted for any annexin in this study. Further analysis showed that each of all four annexin protein possesses a primary structure consisting of a short but variable N-terminal region and a long C-terminal core containing four homologous annexin repeats (I-IV), which contain five alpha-helices. The life cycle expression profile of each annexin was assessed using quantitative PCR. The results showed that the overall transcript levels of the each of four homologous annexins were relatively low in the egg stage, but increased gradually after the transition of cercariae (the invasive schistosome larvae) to schistosomula (the post-invasive larvae). Circular dichroism (CD) demonstrated that rAnnexin B30, rAnnexin B5a and rAnnexin 7a were folded, showing a secondary structure content rich in alpha-helices. The membrane binding affinity was enhanced when rAnnexin B30, rAnnexin B5a and rAnnexin 7a was incubated in the presence of Ca
Publisher: Elsevier BV
Date: 11-2006
DOI: 10.1016/J.EXPPARA.2006.03.003
Abstract: We report the design, fabrication, and validation of a microarray covering the majority of the Schistosoma japonicum and Schistosoma mansoni transcriptomes. The oligonucleotide microarray contains 12,166 S. mansoni and 7055 S. japonicum target sequences. A confidence threshold of <or=0.001 (P value) was used in all analyses. The cross hybridization potential of the microarray was representative of 10,362 probes detected in both channels, while 12,052 probes hybridised to S. japonicum and 11,254 probes hybridised to S. mansoni. Differential hybridisation consisted of 3422 probes to S. mansoni mRNA and 3103 probes to S. japonicum mRNA. Important biological functions, such as transport, metabolism, immune evasion and host-parasite immunological interplay, cell communication, and sexual maturation are represented on this microarray. This is the first microarray commercially manufactured for studying schistosomes, and the large size and verified quality of the resource demonstrate its power for characterising the schistosome transcriptome.
Publisher: Public Library of Science (PLoS)
Date: 09-02-2010
Publisher: Public Library of Science (PLoS)
Date: 06-01-2021
DOI: 10.1371/JOURNAL.PNTD.0008997
Abstract: Scabies, a highly contagious skin disease affecting more than 200 million people worldwide at any time, is caused by the parasitic mite Sarcoptes scabiei . In the absence of molecular markers, diagnosis requires experience making surveillance and control challenging. Superficial microthrombi in the absence of vasculitis in scabies-affected skin are a recognised, yet unexplained histopathological differential of scabies infection. This study demonstrates that a family of Scabies Mite Inactivated Cysteine Protease Paralogues (SMIPP-Cs) excreted by the mites plays a role in formation of scabies-induced superficial microthrombi. A series of in vitro and ex vivo experiments involving two representative recombinant SMIPP-Cs was carried out. In the presence of SMIPP-Cs, the thrombin clotting time (TCT), fibrin formation and plasmin induced fibrinolysis were monitored in vitro . The ultrastructure of the SMIPP-C—modulated fibrin was analysed by Scanning Electron Microscopy (SEM). Immuno-histological analyses were performed ex vivo , to localise the SMIPP-C proteins within scabies infected skin biopsies. SMIPP-Cs displayed pro-coagulant properties. They bound calcium ions, reduced the thrombin clotting time, enhanced the fibrin formation rate and delayed plasmin-induced fibrinolysis. The SMIPP-Cs associated with fibrin clots during fibrinogen polymerisation and did not bind to preformed fibrin. Scanning electron microscopy revealed that the fibrin clots formed in the presence of SMIPP-Cs were aberrant and denser than normal fibrin clots. SMIPP-Cs were detected in microthrombi which are commonly seen in scabietic skin. The SMIPP-Cs are the first scabies mite proteins found in sub-epidermal skin layers and their pro-coagulant properties promote superficial microthrombi formation in scabetic skin. Further research is needed to evaluate their potential as diagnostic or therapeutic target.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.IJPARA.2009.10.008
Abstract: Immunohistochemistry, confocal immunofluorescence and immunogold labelling were used to determine the localisation of the host-protective antigens To16, To18 and To45W in Taenia ovis oncospheres. During maturation of the adult tapeworm the antigens were initially seen as diffuse staining in the developing oncospheres but in mature oncospheres four distinct cells stained positively for the antigens. Confocal fluorescence microscopy using different fluorophores revealed that each of the antigens co-localises within the same cells in the oncosphere. No surface localisation was seen in non-activated or recently activated parasites. Immunogold labelling of non-activated oncosphere sections viewed in transmission electron microscopy revealed labelling of bilateral cells, however the identities of these cells was unclear due to deficiencies in the current level of understanding of oncosphere ultrastructure. Localisation of all the antigens changed dramatically after oncospheres were activated in vitro with each of the antigens being dispersed more generally throughout the parasite parenchyma. During development of the parasites in in vitro culture, surface localisation of the proteins was seen in parasites after 3 or more days in culture. All three antigens were found to be completely absent in parasites by 15 days of culture. The location of the host-protective antigens suggests that initially the invading oncospheres are not susceptible to vaccine-induced antibody and complement mediated attack, but that as the parasites mature, the host-protective antigens come to be associated with the parasite's surface, rendering them susceptible to immune attack.
Publisher: Elsevier BV
Date: 02-2013
DOI: 10.1016/J.MCP.2012.08.005
Abstract: The Chinese (SjC) and Philippine (SjP) strains of the blood fluke Schistosoma japonicum have been shown to present clearly different phenotypes in fecundity, pathology, drug sensitivity and immunology. We used microarray based comparative genomic hybridisation (aCGH) to investigate structural differences in the genomes of the two strains and identified seven distinct regions of the S. japonicum genome that present differential aCGH representing either deletion or duplication regions in SjP. Within these regions, genes predicted to be associated with the recognised phenotypic differences were identified and that may provide new insights into the biology and evolution of the two strains, with implications for the epidemiology and control of schistosomiasis japonica in China and the Philippines.
Publisher: Public Library of Science (PLoS)
Date: 09-03-2010
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.IJPARA.2006.04.015
Abstract: The disease manifestations of schistosomiasis arise from the mammalian host-mediated type 2 T-helper cell-induced (Th2) fibro-granulomatous inflammatory response to eggs trapped within host tissues. Activated hepatic stellate cells are well described as the effector cells of hepatic fibrosis in a variety of human diseases and rodent models. The aim of this study was to further understand the mechanism of fibrosis and the role of hepatic stellate cells in hepatic schistosomiasis progression. Groups of female CBA mice, which produce an intermediate degree of Schistosoma japonicum-induced liver fibrosis, were infected with S. japonicum, perfused at fortnightly time points and the liver tissue and contained egg granulomas examined by immunohistochemistry and cytokine and chemokine analysis using quantitative PCR. Immunohistochemistry demonstrated the presence of activated hepatic stellate cells in the periphery of egg granulomas, adjacent to fibrotic areas. Time course analysis demonstrated that the transcription of smooth muscle actin-alpha type 1 collagen, IL-4, IL-13, IL-13Ralpha2 and tissue inhibitor of metalloproteinase-1 mirrored the initial increase and subsequent down-modulation of granuloma diameter in mice. However, the transcription of monocyte chemo-attractant protein-1, Regulated upon Activation Normal T Cell Expressed and Secreted (RANTES), TNF-alpha, IFN-gamma and matrix metalloproteinase-9 paralleled the evolution of the total liver disease burden. Transforming growth factor-beta1 transcription did not appear to be of biological significance in this mouse model. Immunohistochemical analysis of human hepatic granulomas showed close association of smooth muscle actin-alpha-expressing cells with fibrosis in five available cases of end-stage (advanced) schistosomiasis japonica. We conclude that activated hepatic stellate cells play a contributory role in the granulomatous, fibrotic process induced by S. japonicum eggs, both in the murine model and in human disease.
Publisher: Elsevier BV
Date: 03-1995
DOI: 10.1016/0166-6851(95)00020-2
Abstract: A muscle-specific gene of Echinococcus granulosus has been identified and characterized. A lambda gt11 clone (10P1), containing an incomplete copy of the gene, was originally isolated from a larval E. granulosus cDNA library by serum antibodies from dogs infected with the parasite. The full-length cDNA sequence was obtained by PCR lification of cDNA from an adult E. granulosus lambda gt22A library. Southern blot analysis indicated the presence of the gene as a single copy in the genome of E. granulosus and also detected homologous genes in genomic DNA of E. multilocularis and Taenia saginata. The 21.2-kDa protein deduced from the complete cDNA sequence contains two regions of 12 amino acids with similarity to the EF-hand motif of calcium binding proteins. Antibodies raised against the purified 10P1-GST fusion protein detected a 22-kDa antigen in the E. granulosus developmental stages examined. Immunoelectron microscopy localized the native protein in the muscle of the parasite. The amino-acid sequence of the E. granulosus protein shows significant homology to the muscle proteins mp20 of Drosophila melanogaster, chicken SM22 alpha and mammalian calponin, and also to the neuronal protein NP25 of rats. A conserved carboxy-terminal motif of 17 amino acids is present in all the homologous proteins and is proposed to be the characteristic feature of a novel protein family. The term myophilin is proposed for the E. granulosus protein due to its localization and homology to other muscle proteins.
Publisher: American Chemical Society (ACS)
Date: 07-02-2018
DOI: 10.1021/ACSCHEMNEURO.8B00018
Abstract: Eosinophilic meningitis caused by Angiostrongylus cantonensis is spreading worldwide, and it can manifest as a severe neurological disease. Angiostrongyliasis is a food- and water-borne parasitosis that usually exhibits a seasonal and circumscribed geographical distribution. To improve control and treatment of these infections, further studies of transmission dynamics under natural conditions and the development of better diagnostic tools and treatment options are needed.
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.IJPARA.2021.11.002
Abstract: The unique multilaminate appearance of the tegument surface of schistosomes was first described in 1973, in one of the earliest volumes of the International Journal for Parasitology. The present review, published almost 50 years later, traces the development of our knowledge of the tegument, starting with those earliest cytological advances, particularly the surface plasma membrane-membranocalyx complex, through an era of protein discovery to the modern age of protein characterization, aided by proteomics. More recently, analysis of single cell transcriptomes of schistosomes is providing insight into the organisation of the cell bodies that support the surface syncytium. Our understanding of the tegument, notably the nature of the proteins present within the plasma membrane and membranocalyx, has provided insights into how the schistosomes interact with their hosts but many aspects of how the tegument functions remain unanswered. Among the unresolved aspects are those concerned with maintenance and renewal of the surface membrane complex, and whether surface proteins and membrane components are recycled. Current controversies arising from investigations about whether the tegument is a source of extracellular vesicles during parasitism, and if it is covered with glycolytic enzymes, are evaluated in the light of cytological and proteomic knowledge of the layer.
Publisher: Springer Science and Business Media LLC
Date: 1992
DOI: 10.1007/BF00931577
Publisher: Elsevier
Date: 2016
DOI: 10.1016/BS.APAR.2015.12.002
Abstract: Zoonotic parasitic diseases are increasingly impacting human populations due to the effects of globalization, urbanization and climate change. Here we review the recent literature on the most important helminth zoonoses, including reports of incidence and prevalence. We discuss those helminth diseases which are increasing in endemic areas and consider their geographical spread into new regions within the framework of globalization, urbanization and climate change to determine the effect these variables are having on disease incidence, transmission and the associated challenges presented for public health initiatives, including control and elimination.
Publisher: American Society of Microbiology
Date: 2019
Publisher: Bentham Science Publishers Ltd.
Date: 11-2008
DOI: 10.2174/138945008786786136
Abstract: Microarrays are a platform resource that allow the analysis of the entire transcriptome profile of an organism. New advances in the design and production phases make microarrays the perfect tool for parasitology. The mode of action of many drugs employed to treat parasitic diseases are not understood and coupled with rising concerns of drug resistance, all emphasises the importance of research into the interactions drugs have on their target transcriptomes. One particular disease schistosomiasis, relies on a limited number of chemotherapies for treatment and is a prime ex le of the need for detailed gene expression information while under drug pressure. Recent microarray studies investigating the basic biology of the major species of Schistosoma and their associated microarray platforms, have provided the basis for future drug mode of action/ drug resistance studies. However determining what is a direct gene expression change due to drug treatment is a hurdle that must be addressed both at the level of parasitology and general toxicology. The utilisation of time-course and/or drug concentration studies, and generic stress inducers, in combination with advanced statistical/bioinformatical methods will allow the separation of direct, indirect and generic gene expression responses. It is hoped that with these approaches the future investigation of complex biological and physiological questions such as drug mode of action or drug resistance in parasitology may be addressed.
Publisher: Public Library of Science (PLoS)
Date: 27-01-2022
DOI: 10.1371/JOURNAL.PONE.0263188
Abstract: Schistosomiasis is a neglected tropical parasitic and chronic disease affecting hundreds of millions of people. Adult schistosomes reside in the blood stream of the definitive mammalian host. These helminth parasites possess two epithelial surfaces, the tegument and the gastrodermis, both of which interact with the host during immune evasion and in nutrient uptake. Female ARC Swiss mice (4–6 weeks old) were infected percutaneously with Schistosoma japonicum cercariae freshly shed from Oncomelania hupensis quadrasi snails (Philippines strain). Fluorescent in situ hybridisation (FISH) was performed by using fresh adult S . japonicum perfused from those infected mice. Adult S . japonicum worms were processed to isolate the tegument from the carcass containing the gastrodermis blood and bile were collected in idually from infected and uninfected mice. Total DNA extracted from all those s les were used for microbiome profiling. FISH and microbiome profiling showed the presence of bacterial populations on two epithelial surfaces of adult worms, suggesting they were distinct not only from the host blood but also from each other. Whereas microbial ersity was reduced overall in the parasite epithelial tissues when compared with that of host blood, specific bacterial taxa, including Anoxybacillus and Escherichia , were elevated on the tegument. Minimal differences were evident in the microbiome of host blood during an active infection, compared with that of control uninfected blood. However, s ling of bile from infected animals identified some differences compared with controls, including elevated levels of Limnohabitans , Clostridium and Curvibacter . Using FISH and microbial profiling, we were able to demonstrate, for the first time, that bacteria are presented on the epithelial surfaces of adult schistosomes. These schistosome surface-associated bacteria, which are distinct from the host blood microenvironment, should be considered as a new and important component of the host-schistosome interaction. The importance of in idual bacterial species in relation to schistosome parasitism needs further elucidation.
Publisher: Springer Science and Business Media LLC
Date: 20-11-2014
Publisher: Springer Science and Business Media LLC
Date: 29-03-2006
DOI: 10.1007/S00018-005-5578-1
Abstract: The schistosomulum is the main target of vaccine-induced protective immunity however, most studies have utilized schistosomula produced by mechanical transformation of infective larvae followed by in vitro culture rather than larvae isolated directly from the lungs of infected mammals. Using transmission electron microscopy, we demonstrated that there was little difference in the ultrastructure of Schistosoma japonicum schistosomula obtained by the two methods. However, significant differences in gene expression profiles were apparent when we used an oligonucleotide microarray to compare the gene expression profiles of schistosomula obtained in vivo from lung tissue with those maintained in vitro, and with adult worms of S. japonicum. It is likely that host environmental factors, which cannot be reliably reproduced in vitro, do influence the growth, development and overall biology of schistosomes. Thus caution is urged when using in vitro-cultured schistosomes and mechanically transformed/cultured schistosomula in molecular, biochemical and immunological studies.
Publisher: Informa UK Limited
Date: 03-2001
Publisher: MDPI AG
Date: 23-10-2017
Publisher: Frontiers Media SA
Date: 13-01-2023
DOI: 10.3389/FIMMU.2022.1105719
Abstract: Employing the flatworm parasite Schistosoma mansoni as a model, we report the first application of CRISPR interference (CRISPRi) in parasitic helminths for loss-of-function studies targeting the SmfgfrA gene which encodes the stem cell marker, fibroblast growth factor receptor A (FGFRA). SmFGFRA is essential for maintaining schistosome stem cells and critical in the schistosome-host interplay. The SmfgfrA gene was targeted in S. mansoni adult worms, eggs and schistosomula using a catalytically dead Cas9 (dCas9) fused to a transcriptional repressor KRAB. We showed that SmfgfrA repression resulted in considerable phenotypic differences in the modulated parasites compared with controls, including reduced levels of SmfgfrA transcription and decreased protein expression of SmFGFRA, a decline in EdU (thymidine analog 5-ethynyl-2’-deoxyuridine, which specifically stains schistosome stem cells) signal, and an increase in cell apoptosis. Notably, reduced SmfgfrA transcription was evident in miracidia hatched from SmfgfrA -repressed eggs, and resulted in a significant change in miracidial behavior, indicative of a durable repression effect caused by CRISPRi. Intravenous injection of mice with SmfgfrA -repressed eggs resulted in granulomas that were markedly reduced in size and a decline in the level of serum IgE, emphasizing the importance of SmFGFRA in regulating the host immune response induced during schistosome infection. Our findings show the feasibility of applying CRISPRi for effective, targeted transcriptional repression in schistosomes, and provide the basis for employing CRISPRi to selectively perturb gene expression in parasitic helminths on a genome-wide scale.
Publisher: Public Library of Science (PLoS)
Date: 30-07-2020
Publisher: Public Library of Science (PLoS)
Date: 30-06-2009
Publisher: No publisher found
Date: 2001
Abstract: Echinobothrium chisholmae n. sp. is described from Rhinobatos typus Bennett (Rhinobatidae), collected from Heron Island, Great Barrier Reef, Australia. E. chisholmae differs from all congeners in possessing 11 hooks in each dorsal and ventral group on the rostellum and groups of 3-6 hooklets on either side of the hooks. A single metacestode of E. chisholmae was collected from the decapod crustacean Penaeus longistylus Kubo. Yellow pigmentation of the cephalic peduncle in immature adults is caused by the accumulation of large vesicles in the distal cytoplasm of the tegument. The vesicles probably provide materials for spine formation. Ultrastructural examination of the rostellar musculature revealed that the muscles are stratified (striated-like), consisting of a periodic repetition of sarcomeres separated by perforated Z-like lines that are oblique to the long axes of the myofilaments.
Publisher: Elsevier BV
Date: 05-1997
DOI: 10.1016/S0020-7519(97)00007-6
Abstract: The egg cell forming region of Gyrodactylus kobayashii from goldfish (Carassius auratus) is a thin nucleated cytoplasmic layer surrounding the developing egg cell (= oocyte). The cytoplasm contains numerous elougate membranes. As parasites age, the egg cell forming region becomes electron lucent. The apical membrane of the egg cell forming region becomes disrupted in places. A basal matrix is indistinct in new-born and young worms, becoming more evident as worms grow older. Numerous pits (= basal pits) are found along the basal plasma membrane of worms with a mature male system. These pits appear to be stable components of the membrane and resemble hemidesmosomes. Basal pits were co-incident with sperm in the egg cell forming region in 3 of 5 worms examined. The function of the basal pits of G. kobayashii could not be determined. It is postulated, however, that they either assist sperm to traverse the egg cell forming region to fertilize the egg cell or stabilize the egg cell forming region against damage by sperm traversing this layer. The egg cell forming region encloses a large egg cell and 1 or more smaller differentiating egg cells. The ripening egg cell has a large nucleus and extensive cytoplasm. The cell has a thickened membrane. Large vacuoles and invaginations at the periphery of the egg cell appear to engulf cytoplasm of the egg cell forming region.
Publisher: Springer Science and Business Media LLC
Date: 02-2002
Publisher: Springer Science and Business Media LLC
Date: 18-11-2010
Abstract: Hemoparasites, like malaria and schistosomes, are constantly faced with the challenges of storing and detoxifying large quantities of heme, released from their catabolism of host erythrocytes. Heme is an essential prosthetic group that forms the reactive core of numerous hemoproteins with erse biological functions. However, due to its reactive nature, it is also a potentially toxic molecule. Thus, the acquisition and detoxification of heme is likely to be paramount for the survival and establishment of parasitism. Understanding the underlying mechanism involved in this interaction could possibly provide potential novel targets for drug and vaccine development, and disease treatment. However, there remains a wide gap in our understanding of these mechanisms. This review summarizes the biological importance of heme for hemoparasite, and the adaptations utilized in its sequestration and detoxification.
Publisher: Public Library of Science (PLoS)
Date: 16-07-2008
Publisher: Springer Science and Business Media LLC
Date: 03-2003
DOI: 10.1007/S00441-002-0687-8
Abstract: Cestodes (tapeworms) are a derived, parasitic clade of the phylum Platyhelminthes (flatworms). The cestode body wall represents an adaptation to its endoparasitic lifestyle. The epidermis forms a non-ciliated syncytium, and both muscular and nervous system are reduced. Morphological differences between cestodes and free-living flatworms become apparent already during early embryogenesis. Cestodes have a complex life cycle that begins with an infectious larva, called the oncosphere. In regard to cell number, cestode oncospheres are among the simplest multicellular organisms, containing in the order of 50-100 cells. As part of our continuing effort to analyze embryonic development in flatworms, we describe here the staining pattern obtained with acTub in embryos and larvae of the cestode Hymenolepis diminuta and, briefly, the monogenean Neoheterocotyle rhinobatidis. In addition, we labeled the embryonic musculature of Hymenolepis with phalloidin. In Hymenolepis embryos, two different cell types that we interpret as neurons and epidermal gland cells express acTub. There exist only two neurons that develop close to the midline at the anterior pole of the embryo. The axons of these two neurons project posteriorly into the center of the oncosphere, where they innervate the complex of muscles that is attached to the hooklets. In addition to neurons, acTub labels a small and invariant set of epidermal gland cells that develop at superficial positions, anteriorly adjacent to the neurons, in the dorsal midline, and around the posteriorly located hooklets. During late stages of embryogenesis they spread and form a complete covering of the embryo. We discuss these data in the broader context of platyhelminth embryology.
Publisher: Elsevier BV
Date: 09-2014
DOI: 10.1016/J.MOLBIOPARA.2014.08.002
Abstract: The intestinal tract of schistosomes opens at the mouth and leads into the foregut or oesophageal region that is lined with syncytium continuous with the apical cytoplasm of the tegument. The oesophagus is surrounded by a specialised gland, the oesophageal gland. This gland releases materials into the lumen of the oesophagus and the region is thought to initiate the lysis of erythrocytes and neutralisation of immune effectors of the host. The oesophageal region is present in the early invasive schistosomulum, a stage potentially targetable by anti-schistosome vaccines. We used a 44k oligonucleotide microarray to identify highly up-regulated genes in microdissected frozen sections of the oesophageal gland of male worms of S. mansoni. We show that 122 genes were up-regulated 2-fold or higher in the oesophageal gland compared with a whole male worm tissue control. The enriched genes included several associated with lipid metabolism and transmembrane transport as well as some micro-exon genes. Since the oesophageal gland is important in the initiation of digestion and the fact that it develops early after invasion of the mammalian host, further study of selected highly up-regulated functionally important genes in this tissue may reveal new anti-schistosome intervention targets for schistosomiasis control.
Publisher: Frontiers Media SA
Date: 22-06-2022
DOI: 10.3389/FIMMU.2022.868077
Abstract: Stem cells play significant roles in driving the complex life cycle of Schistosoma mansoni . Fibroblast growth factor (FGF) receptor A (SmFGFRA) is essential for maintaining the integrity of schistosome stem cells. Using immunolocalization, we demonstrated that SmFGFRA was distributed abundantly in germinal/stem cells of different S. mansoni life stages including eggs, miracidia, cercariae, schistosomula and adult worms. Indeed, SmFGFRA was also localized ly in embryonic cells and in the perinuclear region of immature eggs von Lichtenberg’s layer and the neural mass of mature eggs the ciliated surface and neural mass of miracidia the tegument cytosol of cercariae, schistosomula and adult worms and was present in abundance in the testis and vitellaria of adult worms of S. mansoni . The distribution pattern of SmFGFRA illustrates the importance of this molecule in maintaining stem cells, development of the nervous and reproductive system of schistosomes, and in the host-parasite interplay. We showed SmFGFRA can bind human FGFs, activating the mitogen activated protein kinase (MAPK) pathway of adult worms in vitro . Inhibition of FGF signaling by the specific tyrosine kinase inhibitor BIBF 1120 significantly reduced egg hatching ability and affected the behavior of miracidia hatched from the treated eggs, emphasizing the importance of FGF signaling in driving the life cycle of S. mansoni . Our findings provide increased understanding of the complex schistosome life cycle and host-parasite interactions, indicating components of the FGF signaling pathway may represent promising targets for developing new interventions against schistosomiasis.
Publisher: Wiley
Date: 25-06-2010
DOI: 10.1111/J.1365-3024.2010.01241.X
Abstract: SerpinB2, also known as plasminogen activator inhibitor type‐2, is a major product of macrophages and is upregulated during many infections. Although SerpinB2 inhibits urokinase plasminogen activator in vitro , evidence that this represents its physiological role in vivo is not compelling. We have recently shown that SerpinB2 −/− mice generate enhanced Th1 responses after immunization with a Th1 immunogen. Herein, we show that Schistosoma japonicum granulomas induced liver SerpinB2 mRNA expression by ‐fold in wild‐type mice. In SerpinB2 −/− mice, worm and egg burden, and granuloma number and volume were unaffected. However, granulomas in these mice were associated with reduced fibrosis (as determined by Sirius red staining and image analysis) and increased iNOS, IL‐6, IL‐10 and TNFα and decreased Arg 1 and IL‐13 mRNA expression. SerpinB2 −/− mice immunized with soluble egg antigen (SEA) also showed reduced levels of SEA‐specific IgG1. SerpinB2 deficiency thus promoted certain Th1 and reduced certain Th2 responses in response to this Th2 immunogen.
Publisher: Elsevier BV
Date: 06-1998
DOI: 10.1016/S0020-7519(98)00055-1
Abstract: Eucestodes have a simple aceolomate body structure and are conservative in terms of the numbers and nature of their cell types. Nevertheless, the cestodes form a erse group with many strikingly different forms distinguished by the structure of their holdfasts, sexual tissues and embryos. These morphological adaptations have their origins in subtle variations in the structure of their cells and extracellular matrices. This review is concerned with the biology of eucestode epithelia and examines their structure and functions, interrelationships with other tissues, and gives insight into how their components are modified among the many taxa. Three features of cestode epithelia, namely, the occurrence of regional specialisation, microtriches and secretory components, are described. In addition, evidence is presented to suggest that some cestode epithelia are involved in developmental processes such as the nurture of embryos and maintenance of surrounding tissues.
Publisher: Elsevier BV
Date: 02-1995
DOI: 10.1016/S0040-8166(95)80008-5
Abstract: Pore channels occur along the grooves of lactic acid-receptive grooved pegs on the antennae of female Aedes aegypti. There are about 38 pore openings per groove or about 456 per peg. This finding is in conflict with the previous report that pore channels were extremely rare. The pore channels are of a similar electron density to the cuticle of the peg, making them difficult to see. For this reason many of the pore channels were probably overlooked in the previous study. We could not find a terminal pore in the grooved peg as has been reported. Scanning electron microscopy and negative staining of the pegs revealed a tip of variable shape, usually without a pore. It is possible that 'edge effect' (more secondary electrons escape from edges of objects, making them appear brighter than central regions) leads to an apparent terminal pore. Occasionally pegs have a number of small (20-40 nm) pores in the tip region and these might also have been misinterpreted as a terminal pore. Pore channels appear to be the primary means of entry for air-borne stimuli in these grooved pegs.
Publisher: Elsevier BV
Date: 07-2001
DOI: 10.1016/S1383-5769(01)00060-5
Abstract: Calponins are proteins present in vertebrate smooth musculature where they occur in association with thin myofilaments. Calponins are not present in vertebrate or invertebrate striated muscles. The blood fluke Schistosoma japonicum expresses a 38.3-kDa protein that bears substantial homology with vertebrate calponin and occurs entirely within smooth musculature of adults. Calponin-like immunoreactivity has been demonstrated in smooth muscles of many invertebrate phyla. The Schistosoma japonicum calponin has been localised in smooth myofibrils of adults where it is associated with myofilaments and sarcoplasmic reticulum. In this study, the ultrastructural localisation of the protein in muscles of S. japonicum cercariae is described. The protein is present in smooth muscles of the forebody and the stratified muscle of the tail. Within the stratified layer, the protein occurs predominantly in transverse arrays of sarcoplasmic reticulum. The localisation data suggest that the calponin-like protein of S. japonicum is involved in contraction of the stratified tail muscle. Furthermore, the presence of a calponin system in the stratified muscle suggests that this muscle is simply a superior form of muscle, closely related to smooth muscles that use a caldesmin-calponin system in contraction.
Publisher: Oxford University Press (OUP)
Date: 10-2006
DOI: 10.1086/506622
Abstract: Dogs are pivotal in Echinococcus granulosus transmission to humans, and dog vaccination provides a very practical and cost-effective prevention strategy. We vaccinated dogs with soluble native proteins isolated from protoscoleces of E. granulosus and induced significant suppression of worm growth and egg production. Accordingly, we tested for vaccine efficacy using recombinant proteins derived from a developmentally regulated gene family (egM) specifically expressed in mature adult E. granulosus worms. Three egM genes--egM4, egM9, and egM123--were subcloned into an expression vector that expressed the molecules as soluble glutathione S-transferase (GST) fusion proteins in Escherichia coli. The 3 fusion proteins were purified for dog vaccination trials (3 doses of 80 microg rotein/dog) in which the dogs were challenged and then necropsied 45 days after infection. Compared with worms in the control dogs that received GST, the 3 recombinant proteins induced a very high level of protection (97%-100%) in terms of suppression of worm growth and, especially, of egg development and embryogenesis. We have thus shown that vaccination of the dog host against E. granulosus is feasible when recombinant proteins are used. Because the egg stage is crucial in the echinococcal life cycle, successful suppression of egg development by vaccination would halt transmission to intermediate hosts, thereby effecting long-term control.
Publisher: Springer Science and Business Media LLC
Date: 10-06-2016
Publisher: Elsevier BV
Date: 05-2014
Publisher: Elsevier BV
Date: 06-2017
DOI: 10.1016/J.EXPPARA.2017.04.001
Abstract: A diagnostic test that is reliable, sensitive, and applicable in the field is extremely important in epidemiological surveys, during medical treatment for schistosomiasis, and for the control and elimination of schistosomiasis. The Helmintex (HTX) method is based on the use of magnetic beads to trap eggs in a magnetic field. This technique is highly sensitive, but the screening of fecal s les consumes lots of time, thus delaying the results, especially in field studies. The objective of this work was to determine the effects of incorporation of the detergent Tween-20 into the method in an attempt to decrease the final pellet volume produced by the HTX method as well as the use of ninhydrin to stain the Schistosoma mansoni eggs. We showed that these modifications reduced the final volume of the fecal sediment produced in the last step of the HTX method by up to 69% and decreased the screening time to an average of 10.1 min per s le. The use of Tween 20 and ninhydrin led to a high percentage of egg recovery (27.2%). The data obtained herein demonstrate that the addition of detergent and the use of ninhydrin to the HTX process can optimize the screening step and also improve egg recovery, thus justifying the insertion of these steps into the HTX method.
Publisher: CSIRO Publishing
Date: 2014
DOI: 10.1071/CH14304
Abstract: New interventions against infectious diseases require a detailed knowledge and understanding of pathogen–host interactions and pathogeneses at the molecular level. The combination of the considerable advances in systems biology research with methods to explore the structural biology of molecules is poised to provide new insights into these areas. Importantly, exploring three-dimensional structures of proteins is central to understanding disease processes, and establishing structure–function relationships assists in identification and assessment of new drug and vaccine targets. Frequently, the molecular arsenal deployed by invading pathogens, and in particular parasites, reveals a common theme whereby families of proteins with conserved three-dimensional folds play crucial roles in infectious processes, but in idual members of such families show high levels of specialisation, which is often achieved through grafting particular structural features onto the shared overall fold. Accordingly, the applicability of predictive methodologies based on the primary structure of proteins or genome annotations is limited, particularly when thorough knowledge of molecular-level mechanisms is required. Such instances exemplify the need for experimental three-dimensional structures provided by protein crystallography, which remain an essential component of this area of research. In the present article, we review two ex les of key protein families recently investigated in our laboratories, which could represent intervention targets in the metabolome or secretome of parasites.
Publisher: Elsevier BV
Date: 04-2010
DOI: 10.1016/J.IJPARA.2009.10.002
Abstract: The ability of the mammalian blood fluke Schistosoma japonicum to survive in the inhospitable environment of the mammalian bloodstream can be attributed, at least in part, to its host-exposed outer surface, called the tegument. The tegument is a dynamic organ and is involved in nutrition, immune evasion and modulation, excretion, osmoregulation and signal transduction. Given its importance for parasite survival, proteins exposed to the host at the surface of the tegument are ideal targets for the development of vaccines and drugs. By biotinylating live adult worms and using a combination of OFFGEL electrophoresis and tandem mass spectrometry 54 proteins were identified as putatively host-exposed in S. japonicum. These included glucose transport proteins, an amino permease, a leucine aminopeptidase and a range of transporters, heat shock proteins and novel immune-active proteins. Members of the tetraspanin protein family and a homologue of Sm 29, a tegument membrane protein from Schistosoma mansoni, both effective vaccine antigens in S. mansoni, were also identified. The fate of labelled surface proteins was monitored over time using electron microscopy and revealed that biotinylated proteins were rapidly internalised from the surface of the tegument and trafficked into the cytoplasmic bridges that connect the distal cytoplasm of the tegument to the underlying cell bodies. The results reported herein dramatically increase the number of S. japonicum proteins known to be exposed to the host and, hence, those of interest as therapeutic targets. The ability of the parasite to rapidly internalise proteins at its surface has implications for the development of vaccines and may explain how these parasites are able to avoid the host immune system for long periods of time.
Publisher: MDPI AG
Date: 21-06-2019
Abstract: Blow flies (Diptera: Calliphoridae) and the house fly (Diptera: Muscidae) are filth flies of medical importance, and control of their population is needed. As insecticide applications have resulted in fly resistance, and the exploration of plant essential oils (EOs) has increased against filth flies, this study assessed the combination of EOs with pyrethoids to enhance toxic efficacy. The EOs of five effective plants were screened initially against the house fly (Musca domestica L.). Their chemical constituent was performed using gas chromatography-mass spectrometry (GC-MS) analysis. The main components of Boesenbergia rotunda (Zingiberaceae) rhizome, Curcuma longa (Zingiberaceae) rhizome, Citrus hystrix (Rutaceae) fruit peel, Ocimum gratissimum (Lamiaceae) seed, and Zanthoxylum limonella (Rutaceae) fruit were δ-3-caren (35.25%), β-turmerone (51.68%), β-pinene (26.56%), p-cumic aldehyde (58.21%), and dipentene (60.22%), respectively. The screening test revealed that the three most effective plant EOs were from B. rotunda, C. longa and O. gratissimum, which were selected for the combination with two pyrethroid insecticides (permethrin and deltamethrin), in order to enhance their synergistic efficacy against the blow flies, Chrysomya megacephala Fabricius, Chrysomya rufifacies Macquart, and Lucilia cuprina Wiedemann, and the house fly. Synergistic action was presented in almost all of the flies tested with permenthrin/deltamethrin/EOs mixtures. It was interesting that the combination of deltamethrin with three EOs showed a synergistic effect on all of the tested flies. However, an antagonistic effect was observed in C. megacephala and M. domestica treated with permethrin-B. rotunda and C. megacephala treated with permethrin-O. gratissimum. The LD50 of insecticides decreased when combined with plant EOs. This alternative strategy will be helpful in developing a formula for effective fly control management.
Publisher: Elsevier BV
Date: 12-2003
DOI: 10.1016/S0020-7519(03)00255-8
Abstract: The tegument of the adult blood fluke Schistosoma japonicum is in direct contact with the host blood and immune systems. A comprehensive understanding of the ultrastructure of the tegument is crucial to the understanding of how the parasite maintains itself within the mammalian host. Important functions such as nutritional uptake and immune evasion are suspected functions of the tegument and this review discusses these aspects and presents some insights into some of these crucial functions. Transmission electron microscopy has allowed the identification of ultrastructural features of the adult S. japonicum, some of which differ from the reported features of other schistosome species. Morphological differences within the tegument of the adult S. japonicum are noted between sexes, among different regions of the worms and between aspects along the length of the parasite. Differences included variations in the ultrastructure, size and number of tegumental bodies and mitochondria within the matrix, and differences in the relative area of the apical surface of the tegument. Functions of the various components of the tegument matrix and specialised functions of different regions of the male and female parasites are discussed based on ultrastructural findings and previously reported biochemical and molecular data.
Publisher: Mary Ann Liebert Inc
Date: 03-2015
Abstract: Despite an apparent increase in cases of angiostrongyliasis in humans and animals in Australia, the epidemiology of infection with the two species of Angiostrongylus that co-exist in this country, namely A. cantonensis and A. mackerrasae, is poorly understood. This knowledge gap is particularly important with respect to A. mackerrasae, a species evidently native to Australia, as its ability to cause disease in humans is unknown. Likewise, there is little information on the roles of native and introduced species of rodents and molluscs as hosts of Angiostrongylus species in Australia. This review focuses on the gaps in the knowledge about the two species, highlighting the need for epidemiological and pathogenesis studies on the native lungworm A. mackerrasae.
Publisher: Wiley
Date: 02-02-2011
Abstract: A better understanding of how schistosomes exploit host nutrients, neuro-endocrine hormones and signalling pathways for growth, development and maturation may provide new insights for improved interventions in the control of schistosomiasis. This paper describes recent advances in the identification and characterisation of schistosome tyrosine kinase and signalling pathways. It discusses the potential intervention value of insulin signalling, which may play an important role in glucose uptake and carbohydrate metabolism in schistosomes, providing the nutrients essential for parasite growth, development and, notably, female fecundity. Significant progress has also been made in the characterisation of other schistosome growth factor receptors, such as transforming growth factor beta receptor and epidermal growth factor receptor, and in our understanding of their roles in the host-parasite molecular dialogue and parasite development. The use of parasite signal transduction components as novel vaccine or drug targets may prove invaluable in prevention, treatment and control strategies to combat schistosomiasis.
Publisher: Elsevier BV
Date: 11-2004
Abstract: The new methods of laser microdissection microscopy have received wide acceptance in biology and have been applied in a small number of parasitology investigations. Here, the techniques and applications of laser microdissection microscopy are reviewed with suggestions of how the systems might be used to explore applied questions in parasite molecular biology and host-parasite interactions.
Publisher: Wiley
Date: 29-11-2012
DOI: 10.1038/ICB.2011.97
Abstract: Parasitic diseases cause significant global morbidity and mortality, particularly in underdeveloped regions of the world. Malaria alone causes ~800000 deaths each year, with children and pregnant women being at highest risk. There is no licensed vaccine available for any human parasitic disease and drug resistance is compromising the efficacy of many available anti-parasitic drugs. This is driving drug discovery research on new agents with novel modes of action. Histone deacetylase (HDAC) inhibitors are being investigated as drugs for a range of diseases, including cancers and infectious diseases such as HIV/AIDS, and several parasitic diseases. This review focuses on the current state of knowledge of HDAC inhibitors targeted to the major human parasitic diseases malaria, schistosomiasis, trypanosomiasis, toxoplasmosis and leishmaniasis. Insights are provided into the unique challenges that will need to be considered if HDAC inhibitors are to be progressed towards clinical development as potential new anti-parasitic drugs.
Publisher: MDPI AG
Date: 22-06-2021
DOI: 10.3390/TROPICALMED6030109
Abstract: Schistosomiasis is a common neglected tropical disease of impoverished people and livestock in many developing countries in tropical Africa, the Middle East, Asia, and Latin America. Substantial progress has been made in controlling schistosomiasis in some African countries, but the disease still prevails in most parts of sub-Saharan Africa with an estimated 800 million people at risk of infection. Current control strategies rely primarily on treatment with praziquantel, as no vaccine is available however, treatment alone does not prevent reinfection. There has been emphasis on the use of integrated approaches in the control and elimination of the disease in recent years with the development of health infrastructure and health education. However, there is a need to evaluate the present status of African schistosomiasis, primarily caused by Schistosoma mansoni and S. haematobium, and the factors affecting the disease as the basis for developing more effective control and elimination strategies in the future. This review provides an historical perspective of schistosomiasis in Africa and discusses the current status of control efforts in those countries where the disease is endemic.
Publisher: Wiley
Date: 15-01-2014
DOI: 10.1111/FEBS.12700
Abstract: Schistosomiasis is a major parasitic disease of humans, second only to malaria in its global impact. The disease is caused by digenean trematodes that infest the vasculature of their human hosts. These flukes are limited externally by a body wall composed of a syncytial epithelium, the apical surface membrane of which is a parasitism-adapted dual membrane complex. Annexins are thought to be of integral importance for the stability of this apical membrane system. Here, we present the first structural and immunobiochemical characterization of an annexin from Schistosoma mansoni. The crystal structure of annexin B22 confirms the presence of the previously predicted α-helical segment in the II/III linker and reveals a covalently linked head-to-head dimer. From the calcium-bound crystal structure of this protein, canonical type II, type III and B site positions are occupied, and a novel binding site has been identified. The dimer arrangement observed in the crystal structure suggests the presence of two prominent features, a potential non-canonical membrane binding site and a potential binding groove opposite to the former. Results from transcriptional profiling during development show that annexin B22 expression is correlated with life stages of the parasite that possess the syncytial tegument layer, and ultrastructural localization by immuno-electron microscopy confirms the occurrence of annexins in the tegument of S. mansoni. Data from membrane binding and aggregation assays indicate the presence of differential molecular mechanisms and support the hypothesis of annexin B22 providing structural integrity in the tegument.
Publisher: Cambridge University Press (CUP)
Date: 07-1997
DOI: 10.1017/S0031182097008925
Abstract: This paper describes the first localization study of the 14·7 kDa fatty acid-binding protein in Schistosoma japonicum (Sj-FABPc) using transmission electron microscopy. A polyclonal antibody raised against recombinant Sj-FABPc was used in combination with a colloidal gold marker to determine the distribution of the protein within adult parasites. Sj-FABPc was localized within lipid droplets below the subtegumental region of the male parasite. Additionally, Sj-FABPc was present in the vitelline droplets of the vitelline glands of female parasites. There were no detectable levels of Sj-FABPc on the surface or within the tegument of male or female parasites. Possible functions of Sj-FABPc within S. japonicum and the relevance of these immunolocalization findings in light of the recent reports that the homologue Sm-FABPc is an important anti- S. mansoni vaccine target molecule are also discussed.
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.PARINT.2011.07.014
Abstract: The structure and organization of the nervous system has been documented for various helminth parasites. However, the neuroanatomy of the carcinogenic liver fluke, Opisthorchis viverrini has not been described. This study therefore investigated the organization of the nervous system of this fluke using cholinesterase activity, aminergic and peptidergic (FMRFamide-like peptides) immunostaining to tag major neural elements. The nervous system, as detected by acetylcholinesterase (AchE) reaction, was similar in newly excysted metacercariae, migrating juveniles and adult parasites. In these stages, there were three pairs (dorsal, ventral and lateral) of bilaterally symmetrical longitudinal nerve cords and two cerebral ganglia. The ventral nerve cords and the cerebral ganglia were well-developed and exhibited strong AchE reactivity, as well as aminergic and FMRFamide-like immunoreactivity. Numerous immunoreactive nerve cell bodies were observed around the inner surface of the ventral sucker. Fine FMRFamide-like peptides immunopositive nerve fiber was rarely observed. Overall, the organization of the nervous system of O. viverrini is similar to other trematodes.
Publisher: Springer Science and Business Media LLC
Date: 16-04-2019
Publisher: Wiley
Date: 04-11-2020
Publisher: Elsevier BV
Date: 05-2005
DOI: 10.1016/J.EXPPARA.2005.02.003
Abstract: We describe a method for obtaining improved secondary infections of Echinococcus granulosus that involves culturing protoscolex larvae in vitro prior to inoculation into mice. This approach provides a far superior method for obtaining secondary echinococcosis infections in mice compared with the traditional method of direct inoculation of protoscoleces (PSC) where the majority of parasites are killed by the host. We obtained a high rate of recovery both in terms of secondary cyst numbers and their viability. After 50 weeks post-infection (p.i.), brood capsules were formed and the first PSC developed in each of the capsules. After 56 weeks p.i., the fastest developing brood capsule contained four PSC. The approach will prove valuable for investigating parasite development and the host-parasite interaction in secondary echinococcosis.
Publisher: JSTOR
Date: 02-1985
DOI: 10.2307/3281969
Publisher: CSIRO Publishing
Date: 1988
DOI: 10.1071/ZO9880545
Abstract: The development of embryonic envelopes and paruterine capsules in Cylindrotaenia hickmani (Jones 1985) Jones, 1987 were studied using transmission electron microscopy. The embryonic envelopes of C. hickmani form in a similar way to those of other cyclophyllideans. The extant embryonic envelopes in fully developed eggs are: the thin, featureless outer envelope the inner envelope, which forms an oncospheral membrane embryophore and an electron-dense peripheral cytoplasmic layer that lies immediately internal to the external plasma membrane of the inner envelope. Processes of uterine epithelial cells envelop the outer capsule of early embryos. Both the uterine envelope and outer capsule are lost as eggs develop. Paruterine organs are complex, paired structures that form lipid and flattened cellular processes for inclusion within paruterine capsules. Paruterine capsules are complex parenchymal structures containing eggs and the products of the paruterine organs. The possession of such complex paruterine envelopes suggests that the life cycles of nematotaeniids are terrestrial. The sequence of events in paruterine capsule formation in nematotaeniids is unlike that seen in other cyclophyllidean groups with paruterine capsules and it is unlikely that nematotaeniids are closely related to such cestodes.
Publisher: Elsevier BV
Date: 2015
DOI: 10.1016/J.IJPARA.2014.08.011
Abstract: Schistosomiasis is a chronic parasitic disease of humans, with two species primarily causing the intestinal infection: Schistosoma mansoni and Schistosoma japonicum. Traditionally, diagnosis of schistosomiasis is achieved through direct visualisation of eggs in faeces using techniques that lack the sensitivity required to detect all infections, especially in areas of low endemicity. A recently developed method termed Helmintex™ is a very sensitive technique for detection of Schistosoma eggs and exhibits 100% sensitivity at 1.3 eggs per gram of faeces, enough to detect even low-level infections. The Helminthex™ method is based on the interaction of magnetic microspheres and schistosome eggs. Further understanding the underlying egg-microsphere interactions would enable a targeted optimisation of egg-particle binding and may thus enable a significant improvement of the Helmintex™ method and diagnostic sensitivity in areas with low infection rates. We investigated the magnetic properties of S. mansoni and S. japonicum eggs and their interactions with microspheres with different magnetic properties and surface functionalization. Eggs of both species exhibited higher binding affinity to the magnetic microspheres than the non-magnetic microspheres. Binding efficiency was further enhanced if the particles were coated with streptavidin. Schistosoma japonicum eggs bound more microspheres compared with S. mansoni. However, distinct differences within eggs of each species were also observed when the distribution of the number of microspheres bound per egg was modelled with double Poisson distributions. Using this approach, both S. japonicum and S. mansoni eggs fell into two groups, one having greater affinity for magnetic microspheres than the other, indicating that not all eggs of a species exhibit the same binding affinity. Our observations suggest that interaction between the microspheres and eggs is more likely to be related to surface charge-based electrostatic interactions between eggs and magnetic iron oxide rather than through a direct magnetic interaction.
Publisher: Elsevier BV
Date: 03-2014
Publisher: Elsevier BV
Date: 07-1997
Abstract: The subcellular locations in infected Vero cells of Kunjin (KUN) virus core protein C and NS4B were analyzed by immunofluorescence (IF) and by immunoelectron microscopy using monospecific antibodies. Selection of appropriate fixation methods for IF showed that both proteins were associated at all times with perinuclear membranes spreading outward in a reticular pattern and they entered the nucleus late during the latent period. Subsequently NS4B was also dispersed through the nucleoplasm, while C appeared in the nucleolus and the nucleoplasm. These nuclear locations were confirmed by immunogold labeling of cryosections of infected cells at 24 hr postinfection. Labeling of NS4B in cryosections was especially enriched in the perinuclear membranes of the endoplasmic reticulum. When C and NS4B were each expressed separately in stably transformed cell lines, both cytoplasmic and nuclear localization was observed by IF and confirmed by immunoelectron microscopy. Thus the two proteins translocated to the nucleus independently of each other and of other viral proteins. Dual IF with antibodies to double-stranded RNA showed that cytoplasmic locations of C and NS4B were apparently associated in part with the sites of viral RNA synthesis which were resistant to solubilization by Triton X-100.
Publisher: Elsevier BV
Date: 05-2014
DOI: 10.1016/J.BIOCEL.2014.03.003
Abstract: Hookworm activation-associated secreted proteins can be structurally classified into at least three different groups. The hallmark feature of Group 1 activation-associated secreted proteins is a prominent equatorial groove, which is inferred to form a ligand binding site. Furthermore, a conserved tandem histidine motif is located in the centre of the groove and believed to provide or support a yet to be determined catalytic activity. Here, we report three-dimensional crystal structures of Na-ASP-2, an L3-secreted activation-associated secreted protein from the human hookworm Necator americanus, which demonstrate transition metal binding ability of the conserved tandem histidine motif. We further identified moderate phosphohydrolase activity of recombinant Na-ASP-2, which relates to the tandem histidine motif. By panning a random 12-mer peptide phage library, we identified a peptide with high similarity to the human calcium-activated potassium channel SK3, and confirm binding of the synthetic peptide to recombinant Na-ASP-2 by differential scanning fluorimetry. Potential binding modes of the peptide to Na-ASP-2 were studied by molecular dynamics simulations which clearly identify a preferred topology of the Na-ASP-2:SK3 peptide complex.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Wiley
Date: 13-08-2015
DOI: 10.1111/FEBS.13368
Abstract: Schistosomes ingest host erythrocytes, liberating large quantities of haem. Despite its toxicity, haem is an essential factor for numerous biological reactions, and may be an important iron source for these helminths. We used a fluorescence haem analogue, palladium mesoporphyrin, to investigate pathways of haem acquisition, and showed that palladium mesoporphyrin accumulates in the vitellaria (eggshell precursor glands) and ovary of female Schistosoma mansoni. Furthermore, incubation of adult females in 10-100 μm cyclosporin A (IC50 = 2.3 μm) inhibits the uptake of palladium mesoporphyrin to these tissues, with tenfold reductions in fluorescence intensity of the ovary. In vitro exposure to cyclosporin A resulted in significant perturbation of egg production, reducing egg output from 34 eggs per female to 5.7 eggs per female over the incubation period, and retardation of egg development. We characterized a S. mansoni homologue of the haem-responsive genes of Caenorhabditis elegans. The gene (Smhrg-1) encodes a protein with a molecular weight of approximately 17 kDa. SmHRG-1 was able to rescue growth in haem transport-deficient HEM1Δ yeast. Transcriptional suppression of Smhrg-1 in adult S. mansoni worms resulted in significant delay in egg maturation, with 47% of eggs from transcriptionally suppressed worms being identified as immature compared with only 27% of eggs laid by control worms treated with firefly luciferase. Our findings indicate the presence of transmembrane haem transporters in schistosomes, with a high abundance of these molecules being present in tissues involved in oogenesis.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2011
Publisher: Wiley
Date: 09-2013
DOI: 10.1002/BIP.22229
Abstract: The risk of reduced sensitivity of the human schistosomes to praziquantel has led to efforts to find new therapies. Here, the cyclotides kalata B1 (kB1), kalata B2 (kB2), MCoCC‐1, and MCoTI‐II, cyclic peptides extracted from plants and shown to be potent against nematodes and insects, were tested for antischistosome activity. In vitro assays showed that high concentrations (500–1000 μ g/mL) of either kB1 or kB2 killed Schistosoma japonicum and Schistosoma mansoni adults within 5 min, whereas MCoTI‐II and MCoCC‐1 had no effect. Lethal concentrations to kill 50% of the population for kB2 was 15.5 ± 7.4 μg/mL at 1 h for male S. japonicum (Philippine strain). Males were more susceptible than females. kB2 showed higher antischistosome activity than kB1 and killing time was concentration‐dependent. Mode of action studies revealed that kB1 and 2 lysed the tegument of adult worms. Lysis of myofibrils was not demonstrated, but longitudinal and radial muscle fibers were distorted, an observation consistent with strong coiling of the parasites after drug exposure. A single dose of kB2 administered either orally or intravenously, reduced worm burdens in S. japonicum‐infected mice from 15% to 60%. However, treatment of S. mansoni‐infected mice did not result in reduction in worm burdens. Our studies show that kB2 acts as a promising antischistosomal against Philippine S. japonicum, and it or other cyclotides may be developed further as general anthelminthics. With thousands of cyclotides predicted to occur in plants, and the amenability of these peptides to combinatorial variation, there is potential for their exploitation as wide‐spectrum anthelminthics. © 2013 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 100: 461–470, 2013.
Publisher: Wiley
Date: 23-12-2015
DOI: 10.1111/BPH.12898
Publisher: Springer Science and Business Media LLC
Date: 1999
Abstract: The structure, abundance, and distribution of tegumentary vesicles was compared among Echinococcus granulosus protoscoleces that had been prepared for electron microscopy using four processing schedules: a conventional method, alternative fixations using uranyl acetate or osmium tetroxide-potassium ferricyanide, and a freeze-substitution method. Four morphologically distinct types of vesicles were found in the somal region. The morphology of the first form, with moderately electron-opaque contents, and the second form, with similar size and shape but containing an electron-opaque core, varied little among the preparation methods. Two additional forms of vesicles, with characteristic intensely electron-opaque contents, were revealed only after freeze-substitution. These elongate vesicles were also found in the scolex tegument where they were most conspicuous, and appeared markedly increased in number after freeze-substitution. Large, spherical vesicles with an electron-lucent core embedded in a dense matrix of fibrillar strands were the dominant vesicle forms in the scolex region after all methods of preparation. Fixation by osmium tetroxide-potassium ferricyanide revealed the presence of spherical vesicles with amorphous electron-opaque contents and a few inclusions. This form of vesicle was also observed after freeze-substitution, but the inclusions in the vesicular lumen were more numerous. The variation in the distribution of vesicle forms among the body regions strongly implies a variety of vesicle functions. In addition, our observations suggest that comparative studies of different fixative methods are necessary to demonstrate the detailed vesicular morphology of the tegument of E. granulosus and other cestodes.
Publisher: MDPI AG
Date: 04-06-2018
Publisher: Elsevier
Date: 2018
DOI: 10.1016/BS.APAR.2018.03.003
Abstract: In this era of increasing demand for sensitive techniques to diagnose schistosomiasis, there is a need for an increased focus on the properties of the parasite eggs. The eggs are not only directly linked to the morbidity of chronic infection but are also potential key targets for accurate diagnostics. Eggs were the primary target of diagnostic tools in the past and we argue they could be the target of highly sensitive tools in the future if we focus on characteristics of their structure and shell surface that could be exploited for enhanced detection. In this review, we discuss the current state of knowledge of the physical structures of schistosome eggs and eggshells with a view to identifying pathways to a comprehensive understanding of their role in the host-parasite relationship and pathogenesis of infection, and pathways to new strategies for development of diagnostics.
Publisher: Elsevier BV
Date: 2007
Publisher: Elsevier BV
Date: 06-2020
Publisher: Public Library of Science (PLoS)
Date: 10-08-2010
Publisher: Wiley
Date: 07-1994
Publisher: Elsevier BV
Date: 11-2003
Publisher: Elsevier BV
Date: 03-2002
DOI: 10.1016/S0020-7519(01)00335-6
Abstract: The Australian cestode fauna remains poorly documented with a total of 342 species recorded to date. The best-studied host groups are the elasmobranchs and the marsupials, but even in these groups, only 32 and 25% of known host species, respectively, have been examined for parasites. Overall, cestodes have been reported from only 5% of the known vertebrate species. Representatives of virtually all cestode orders and most of the cyclophyllidean families have been recorded from Australia. In spite of these deficiencies, some biogeographical patterns are discernible. In the elasmobranchs, a significant proportion of the known cestodes is endemic while other associations exist with eastern Pacific and Indo-west Pacific faunas. Also identifiable is a group of cosmopolitan species. The nematotaeniids of hibians suggest Gondwanan affiliations, while the known proteocephalideans, parasitic in reptiles and hibians, may represent an Asian invasion. Associations of the avian cestodes represent an unexplored but potentially rewarding avenue of biogeographical study. The cestodes of mammals include families with a Gondwanan distribution (Linstowiidae, Hymenolepididae) as well as those (Anoplocephalidae) with an apparent origin in southeast Asia. In addition, a number of genera of cyclophyllidean cestodes (Anoplotaenia, Dasyurotaenia) occurring in marsupials represent biogeographical challenges, not being accommodated within any of the known cestode families. The Australian cestode fauna therefore provides potentially outstanding opportunities for studies of the biogeographical relationships of a number of cestode groups.
Publisher: Oxford University Press (OUP)
Date: 12-2005
DOI: 10.1016/J.TRSTMH.2005.04.020
Abstract: An unusual female case, with alveolar echinococcosis (AE) disseminated from the primary hepatic lesion to the brain by metastasis formation, was retrospectively identified during a community survey in Ningxia Hui Autonomous Region, northwest China in 2003. Among possible metastases of hepatic AE, locations to the brain are rare and usually fatal and they have especially been assigned to concomitant immune suppression. An enhancing role of pregnancy, which may be suspected in this case, the favourable outcome after surgery and chemotherapy, and also a mental disability in a child following long-term intrauterine exposure to mebendazole, make the report particularly unique.
Publisher: Elsevier BV
Date: 09-2001
DOI: 10.1016/S0001-706X(01)00151-6
Abstract: During the course of transmission electron microscopic studies of adult Ancylostoma caninum removed from a dog, several Giardia trophozoites were found in sections of the buccal cavity, oesophagus and intestine of several hookworms. Although the protozoa appeared viable, this unusual finding probably represents accidental uptake by, rather than an established infection of, the hookworm. It is feasible, however, that the trophozoites might have survived and even multiplied in this aberrant site.
Publisher: Canadian Science Publishing
Date: 02-0060
DOI: 10.1139/M95-018
Abstract: Secretions from exocrine metapleural glands of Myrmecia gulosa (Australian bull ant) exhibit broad-spectrum antimicrobial activity. Treatment of the yeast Candida albicans with metapleural secretion resulted in the rapid and total leakage of K + ions from cells within 10 min. Ultrastructural analysis of the bacteria Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa, and cells and protoplasts of Candida albicans demonstrated gross damage of the cell membrane and aggregation of the cytoplasmic matrix of treated cells. Degradation of membrane-bound organelles was also observed in Candida albicans. The antimicrobially active components of metapleural secretions were nonpolar and interacted with the phospholipid bilayer, causing damage to the structural integrity of liposomes and the release of carboxyfluorescein. The data suggest that the antimicrobial agents in metapleural secretion act primarily by disrupting the structure and function of the phospholipid bilayer of the cytoplasmic membrane.Key words: ant metapleural secretion, antimicrobial, Candida albicans, cytoplasmic membrane.
Publisher: Wiley
Date: 09-2010
Abstract: In the last few years, annexins have been discovered in several nematodes and other parasites, and distinct differences between the parasite annexins and those of the hosts make them potentially attractive targets for anti-parasite therapeutics. Annexins are ubiquitous proteins found in almost all organisms across all kingdoms.Here, we present an overview of novel annexins from parasitic organisms, and summarize their phylogenetic and biochemical properties, with a view to using them as drug or vaccine targets. Building on structural and biological information that has been accumulated for mammalian and plant annexins, we describe a predicted additional secondary structure element found in many parasite annexins that may confer unique functional properties, and present a specific antigenic epitope for use as a vaccine.
Publisher: Elsevier BV
Date: 11-2007
DOI: 10.1016/J.EXPPARA.2007.06.004
Abstract: One difficulty facing post-genomic analyses of schistosomes is the limited data on sites of expression of many gene products expressed by the parasites in their hosts. The potential for use of laser microdissection microscopy as a preparative technique for transcriptional and proteomic profiling is reviewed. This technique allows tissues to be dissected for subsequent molecular and protein analysis. The method is reviewed in the light of the acoelomate triploblastic nature of tissue organisation in the parasite.
Publisher: Hindawi Limited
Date: 25-06-2014
DOI: 10.1111/CMI.12316
Abstract: Neutrophils contribute to the pathological processes of a number of inflammatory disorders, including rheumatoid arthritis, sepsis and cystic fibrosis. Neutrophils also play prominent roles in schistosomiasis japonica liver fibrosis, being central mediators of inflammation following granuloma formation. In this study, we investigated the interaction between Schistosoma japonicum eggs and neutrophils, and the effect of eggs on the inflammatory phenotype of neutrophils. Our results showed significant upregulated expression of pro-inflammatory cytokines (IL-1α, IL-1β and IL-8) and chemokines (CCL3, CCL4 and CXCL2) in neutrophils after 4 h in vitro stimulation with S. japonicum eggs. Furthermore, mitochondrial DNA was released by stimulated neutrophils, and induced the production of matrix metalloproteinase 9 (MMP-9), a protease involved in inflammation and associated tissue destruction. We also found that intact live eggs and isolated soluble egg antigen (SEA) triggered the release of neutrophil extracellular traps (NETs), but, unlike those reported in bacterial or fungal infection, NETs did not kill schistosome eggs in vitro. Together these show that S. japonicum eggs can induce the inflammatory phenotype of neutrophils, and further our understanding of the host-parasite interplay that takes place within the in vivo microenvironment of schistosome-induced granuloma. These findings represent novel findings in a metazoan parasite, and confirm characteristics of NETs that have until now, only been observed in response to protozoan pathogens.
Publisher: MDPI AG
Date: 16-08-2018
DOI: 10.3390/IJMS19082426
Abstract: To further investigate the importance of Schistosoma japonicum acetylcholinesterase (SjAChE) in cholinergic signaling for parasite growth and development, we used RNA interference (RNAi) to knock-down its expression in adults and eggs in vitro. This resulted in its reduced transcription but also expression of other important genes involved both in cholinergic signaling and glucose uptake were impacted substantially. Significant decreases in AChE protein expression, AChE enzymatic activity, and glucose uptake were observed in the SjAChE-knockdown parasites compared with luciferase controls. In vaccine/challenge experiments, we found that immunization of mice with recombinant SjAChE (rSjAChE) expressed in Escherichia coli elicited reductions in male worm numbers (33%), liver granuloma density (41%), and reduced numbers of mature intestinal eggs (73%) in the vaccinated group compared with the control group. These results indicate AChE plays an important role in the metabolism of male worms, and impacts indirectly on female fecundity leading to increased numbers of immature eggs being released and reduced sizes of liver granulomas. Furthermore, cytokine analysis showed that immunization of mice with rSjAChE elicited a predominantly Th1-type immune response characterized by increased production of IFNγ in splenic CD4+ T cells of vaccinated mice. The study confirms the potential of SjAChE as a vaccine/drug candidate against zoonotic schistosomiasis japonica.
Publisher: Wiley
Date: 18-12-2020
Publisher: Elsevier BV
Date: 10-2010
DOI: 10.1016/J.IJPARA.2010.04.011
Abstract: The cellular organisation of Taenia ovis oncospheres is interpreted from ultrathin serial sections and transmission electron microscopy following high pressure freezing and freeze-substitution. The surface of a hatched, non-activated T. ovis oncosphere is covered by an oncospheral membrane below which is the tegument bearing microvilli. The basal lamina of the tegument is underlain by broad bands of peripheral somatic musculature. Three pairs of hooks and associated muscles are present in the somatophoric third of the oncosphere. Approximately 19 cells of seven different types were identified which include: (i) a quadri-nucleated syncytium of penetration gland type 1 containing two lateral pairs of cell bodies interconnected by narrow cytoplasmic bridges (PG1) (ii) a quadri-nucleated syncytium of penetration gland type 2 (PG2) (iii) a single-nucleated median mesophoric gland cell (iv) 10 somatic cells (v) two germinative cells (vi) two nerve cells and (vii) a pair of median somatophoric cells. This study provides a clear understanding of the morphology of T. ovis oncospheres and forms the basis for further investigations into the biology of taeniid oncospheres.
Publisher: Cambridge University Press (CUP)
Date: 09-06-2016
DOI: 10.1017/S003118201600069X
Abstract: This study investigated comparatively the pathogenicity of experimental infection of mice and guinea pigs, with Angiostrongylus mackerrasae and the closely related species A. cantonensis . Time course analyses showed that A. mackerrasae causes eosinophilic meningitis in these hosts, which suggests that the species has the potential to cause meningitis in humans and domestic animals. Both A. mackerrasae and the genetically similar A. cantonensis caused eosinophilic meningitis in mice at two time points of 14 and 21 days post infection (dpi). The brain lesions in mice infected with A. mackerrasae were more granulomatous in nature and the parasites were more likely to appear degenerate compared with lesions caused by A. cantonensis . This may indicate that the mouse immune system eliminates A. mackerrasae infection more effectively. The immunologic responses of mice infected with the two Angiostrongylus species was compared by assessing ex vivo stimulated spleen derived T cells and cytokines including interferon-gamma, interleukin 4 and interleukin 17 on 14 and 21 dpi. The results were similar for mice infected with A. cantonensis and A. mackerrasae . Serum from the infected animals with either A. cantonensis or A. mackerrasae recognized total soluble antigen of A. cantonensis female worms on Western blot.
Publisher: Elsevier BV
Date: 03-2014
Abstract: In hepatic schistosomiasis, pathology arises when schistosome eggs become lodged in the host liver, evoking an interleukin 4 (IL-4)- and IL-13-mediated dominant CD4(+) Th2 immune response. This response leads to the development of granulomas and fibrosis, with eosinophils, neutrophils, macrophages, hepatic stellate cells, and lymphocytes all identified as major cellular contributors to these events. This review outlines the cellular and molecular mechanisms of hepatic schistosomiasis, with an emphasis on the major cellular components and their release of chemokines. The differences between Schistosoma mansoni- and Schistosoma japonicum-induced hepatic granuloma are also discussed. This comprehensive overview of the processes associated with hepatic schistosomiasis may provide new insights into improved treatment for both schistosomiasis and other granulofibrotic diseases.
Publisher: Public Library of Science (PLoS)
Date: 11-11-2008
Publisher: Springer Science and Business Media LLC
Date: 04-2022
DOI: 10.1186/S13071-022-05165-2
Abstract: Ixodes barkeri , a tick with a distinctive ventrolateral horn-like projection on palpal segment 1, was described in 2019 from two male ticks from the Wet Tropics of Far North Queensland, Australia. However, females lie at the core of the taxonomy and subgenus classification of Ixodes hence, we sought specimens of female ticks, successfully recovering females, plus nymphs and larvae. Mitochondrial genomes are also desirable additions to the descriptions of species of ticks particularly regarding subgenus systematics. So, we sequenced the mt genomes of I. barkeri Barker, 2019, and the possible relatives of I. barkeri that were available to us ( I. australiensis Neumann, 1904, I. fecialis Warburton & Nuttall, 1909, and I . woyliei Ash et al. 2017) with a view to discovering which if any of the subgenera of Ixodes would be most suitable for I. barkeri Barker, 2019. The female, nymph, larva and mitochondrial genome of Ixodes barkeri Barker, 2019, are described for the first time and the male of I. barkeri is redescribed in greater detail than previously. So far, I. barkeri is known only from a monotreme, the short-beaked echidna, Tachyglossus aculeatus (Shaw, 1792), from the highland rainforests of the Wet Tropics of Far North Queensland, Australia. Our phylogeny from entire mitochondrial genomes indicated that I. barkeri and indeed I. woyliei Ash et al., 2017, another tick that was described recently, are best placed in the subgenus Endopalpiger Schulze, 1935.
Publisher: American Society for Microbiology
Date: 06-2001
DOI: 10.1128/IAI.69.6.3646-3651.2001
Abstract: Schistosoma mansoni masks its surface with adsorbed host proteins including erythrocyte antigens, immunoglobulins, major histocompatibility complex class I, and β 2 -microglobulin (β 2 m), presumably as a means of avoiding host immune responses. How this is accomplished has not been explained. To identify surface receptors for host proteins, we biotinylated the tegument of live S. mansoni adults and mechanically transformed schistosomula and then removed the parasite surface with detergent. Incubation of biotinylated schistosome surface extracts with human immunoglobulin G (IgG) Fc-Sepharose resulted in purification of a 97-kDa protein that was subsequently identified as paramyosin (Pmy), using antiserum specific for recombinant Pmy. Fc also bound recombinant S. mansoni Pmy and native S. japonicum Pmy. Antiserum to Pmy decreased the binding of Pmy to Fc-Sepharose, and no proteins bound after removal of Pmy from extracts. Fluoresceinated human Fc bound to the surface, vestigial penetration glands, and nascent oral cavity of mechanically transformed schistosomula, and rabbit anti-Pmy Fab fragments ablated the binding of Fc to the schistosome surface. Pmy coprecipitated with host IgG from parasite surface extracts, indicating that complexes formed on the parasite surface as well as in vitro. Binding of Pmy to Fc was not inhibited by soluble protein A, suggesting that Pmy does not bind to the region between the CH2 and CH3 domains used by many other Fc-binding proteins. β 2 m did not bind to the schistosome Fc receptor (Pmy), a finding that contradicts reports from earlier workers but did bind to a heteromultimer of labeled schistosomula surface proteins. This is the first report of the molecular identity of a schistosome Fc receptor moreover it demonstrates an additional aspect of the unusual and multifunctional properties of Pmy from schistosomes and other parasitic flatworms.
Publisher: Elsevier BV
Date: 08-2011
DOI: 10.1016/J.EXPPARA.2011.04.006
Abstract: Besides their natural bird hosts, Trichobilharzia regenti cercariae are able to penetrate skin of mammals, including humans. Experimental infections of mice showed that schistosomula of this species are able to avoid the immune response in skin of their non-specific mammalian host and escape the skin to migrate to the CNS. Schistosomula do not mature in mammals, but can survive in nervous tissue for several days post infection. Neuroinfections of specific bird hosts as well as accidental mammalian hosts can lead to neuromotor effects, for ex le, leg paralysis and thus this parasite serves as a model of parasite invasion of the CNS. Here, we show by histological and immunohistochemical investigation of CNS invasion of immunocompetent (BALB/c) and immunodeficient (SCID) mice by T. regenti schistosomula that the presence of parasites in the nervous tissue initiated an influx of immune cells, activation of microglia, astrocytes and development of inflammatory lesions. Schistosomula elimination in the tissue depended on the host immune status. In the absence of CD3+ T-cells in immunodeficient SCID mice, parasite destruction was slower than that in immunocompetent BALB/c mice. Axon injury and subsequent secondary demyelination in the CNS were associated with mechanical damage due to migration of schistosomula through the nervous tissue, and not by host immune processes. Immunoreactivity of the parasite intestinal content for specific antigens of oligodendrocytes/myelin and neurofilaments showed for the first time that schistosomula ingest the nervous tissue components during their migration.
Publisher: JSTOR
Date: 12-1999
DOI: 10.2307/3285667
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.EXPPARA.2016.06.013
Abstract: Infection with the apicomplexan parasite Plasmodium falciparum is a major cause of morbidity and mortality worldwide. One of the striking features of this parasite is its ability to remodel and decrease the deformability of host red blood cells, a process that contributes to disease. To further understand the virulence of Pf we investigated the biochemistry and function of a putative Pf S33 proline aminopeptidase (PfPAP). Unlike other P. falciparum aminopeptidases, PfPAP contains a predicted protein export element that is non-syntenic with other human infecting Plasmodium species. Characterization of PfPAP demonstrated that it is exported into the host red blood cell and that it is a prolyl aminopeptidase with a preference for N-terminal proline substrates. In addition genetic deletion of this exopeptidase was shown to lead to an increase in the deformability of parasite-infected red cells and in reduced adherence to the endothelial cell receptor CD36 under flow conditions. Our studies suggest that PfPAP plays a role in the rigidification and adhesion of infected red blood cells to endothelial surface receptors, a role that may make this protein a novel target for anti-disease interventions strategies.
Publisher: American Society for Microbiology
Date: 23-03-2023
DOI: 10.1128/CMR.00241-21
Abstract: Despite intensive long-term efforts, with very few exceptions, the development of effective vaccines against parasitic infections has presented considerable challenges, given the complexity of parasite life cycles, the interplay between parasites and their hosts, and their capacity to escape the host immune system and to regulate host immune responses. For many parasitic diseases, conventional vaccine platforms have generally proven ill suited, considering the complex manufacturing processes involved and the costs they incur, the inability to posttranslationally modify cloned target antigens, and the absence of long-lasting protective immunity induced by these antigens.
Publisher: Oxford University Press (OUP)
Date: 04-2008
DOI: 10.1016/J.TRSTMH.2008.01.007
Abstract: Cystic echinococcosis (CE), caused by Echinococcus granulosus, and alveolar echinococcosis (AE), due to E. multilocularis, are endemic to large areas of north and northwest China. Here we review features of a severe focus of AE and CE in Ningxia Hui Autonomous Region (NHAR), northwest China. We describe for NHAR the results of surveys of hospital surgical and clinical records, including treatment of AE and CE, and active community detection of asymptomatic/early-stage cases and patient follow-up using questionnaire analysis, ultrasound examinations and serology. We compare the key risk factors for both AE and CE in this setting with those reported from other areas. In addition, we document the socio-economic factors impacting on treatment and control of AE and CE. This update indicates that echinococcosis continues to be highly endemic in NHAR and exemplifies the serious public health problem that the disease presents, particularly in poor rural areas. Extensive community surveys of echinococcosis are required throughout northwest China, especially in rural communities. These will enable earlier detection of echinococcosis cases, thereby improving treatment outcomes, and reveal the true epidemiological picture regarding the disease in this region, with a view to developing and implementing new strategies for future control.
Publisher: Springer Science and Business Media LLC
Date: 09-2000
Abstract: Prochristianella spinulifera n. sp. (Cestoda: Trypanorhyncha: Eutetrarhynchidae) is described from the spiral valves of the rays Rhinobatos typus (Rhinobatidae) and Himantura fai (Dasyatidae) from Heron Island, Queensland, Australia. The new species is distinguished from all congeners by the deltoid microtriches covering the anterior 80% of the scolex and the presence of a dorsoventrally elongate genital atrium. The species occurred in the anteriormost section of the spiral valve of R. typus. The orientation of the armature of this and other congeners is such that principal rows of hooks begin on the bothridial surface of the tentacle and end on the antibothridial surface.
Publisher: Springer Science and Business Media LLC
Date: 15-10-2014
DOI: 10.1007/S00436-014-4153-9
Abstract: The uterine organization in Tetrabothrius erostris (Tetrabothriidea) was investigated by the methods of transmission and scanning electron microscopy. In sexually mature proglottids, the uterine wall consists of a syncytial epithelium (1.4-2.5 μm thick, except in regions containing nuclei). The ribosomes, mitochondria and numerous cisternae of granular endoplasmic reticulum with concentric or parallel profiles with electron lucent material are observed in the epithelium. The uterine wall is characterized by the abundance of lipid droplets that are localized inside the long protrusions of the uterine epithelium (called fungiform papillae) up to 15-17 μm and in the surrounding medullary parenchyma. The protrusions with lipid droplets in the proximal ends of the uterus are located closely to each other. A basal matrix (up to 0.6 μm thick) supports the uterine epithelium. The musculature consisting of 1-2 muscle layers is well developed large myocytons are connected with the myofibrils and have a nucleus that reaches 4 μm in size. In gravid proglottids, the epithelium without nuclei is reduced to 0.2-1.6 μm thick. The number of protrusions of the uterine epithelium and lipid droplets in the epithelial layer decreases. Sparse small muscle bundles underlay the uterine wall at this stage the basal matrix is feebly marked. The matrotrophy or the support by nutrition from the parent organism to embryos is discussed for T. erostris which belongs to oligolecital cestodes and possesses numerous lipid droplets in the uterine wall during the development of embryos.
Publisher: Elsevier BV
Date: 05-1992
DOI: 10.1016/0300-9629(92)90016-J
Abstract: 1. The cloacal and bucco-pharyngeal regions of three species of Australian freshwater turtles were experimentally compared for their ability to take up radiocalcium directly from the aquatic medium. 2. The cloacal route was at least 4 times more important than the bucco-pharyngeal route for radiocalcium uptake, in each of the three species investigated. 3. Histological examination of anatomical regions in the cloaca showed that the cloacal bursae of three species (E. dentata, C. longicollis and E. signata) had abundant villi and infolded mucosal epithelia that increase the surface area of the epithelium exposed to the aquatic medium. 4. Electron microscopic studies on the mucosal epithelium of the cloacal bursae showed that it contained many structural characteristics indicative of an exchange function and consistent with the cloacal bursae being an important site of radiocalcium uptake within the cloaca.
Publisher: Public Library of Science (PLoS)
Date: 18-05-2010
Publisher: Public Library of Science (PLoS)
Date: 24-03-2010
Publisher: Springer Science and Business Media LLC
Date: 28-11-2014
DOI: 10.1007/S00436-013-3671-1
Abstract: Uterine organization and interaction with developing eggs in Tetrabothrius erostris (Tetrabothriidea), Nippotaenia mogurndae (Nippotaeniidea), Arostrilepis tenuicirrosa, and Monocercus arionis (Cyclophyllidea), cestodes belonging to three different orders, were investigated by scanning electron microscopy. The interactions were traced from sexually mature to gravid proglottids for all species. Pieces of evidence of interactions among these species include specific tight contacts between microlamellae of the uterine epithelium and the egg capsule, networks of fibrils between eggs and uterus, or numerous branched erticula of the uterine wall that surround eggs or combinations of these. The contacts between uterine epithelium and eggs take place in mature and post-mature proglottids, at a period of development when eggs are newly formed and the embryos are rapidly developing. The eggs grow and develop actively in tight contact with the uterine wall. The maximum diameter of eggs increases 1.5-2 times (or 3.5-4 times in M. arionis) during development. In all species, the intimate contacts between uterus and eggs have weakened or disappeared by the time the proglottids have become gravid. The association between uterus and eggs thus appears as strong evidence of active trophic interaction (or matrotrophy) between the parent organism and developing eggs.
Publisher: Elsevier BV
Date: 11-1998
DOI: 10.1016/S0020-7519(98)00120-9
Abstract: Ultrastructural details of reproductive epithelia in the viviparous monogenean Gyrodactylus kobayashii are described. Specimens of G. kobayashii were fixed for transmission electron microscopy in glutaraldehyde in sodium cacodylate buffer followed by either 1% aqueous osmium tetroxide or 1% aqueous osmium tetroxide reduced with 1.5% potassium ferricyanide. All reproductive epithelia are underlain by a fibrillar basal matrix. The uterine basal matrix is electron-opaque after potassium ferricyanide reduced osmium tetroxide fixation suggesting the presence of carbohydrate-containing materials. With potassium ferricyanide reduced osmium tetroxide fixation, two prominent membrane systems were distinguished in the uterine epithelium. Basal invaginations are short infoldings of the basal membrane. The basal invaginations are common in other reproductive epithelia and tegument and probably enhance transport of materials by these epithelia. Laminated membranes are membrane stacks, resembling endoplasmic reticulum stacks. These membranes were abundant at the apical membrane. The birth plug is a solid cytoplasmic layer, lacking a lumen, and rich in cytoplasmic vesicles. This layer connects the tegument and the uterine epithelium.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/270756
Publisher: Springer Science and Business Media LLC
Date: 12-1987
DOI: 10.1007/BF00145034
Publisher: Public Library of Science (PLoS)
Date: 23-01-2019
Publisher: American Chemical Society (ACS)
Date: 16-11-2006
DOI: 10.1021/JM061012J
Abstract: The malarial parasite Plasmodium falciparum depends on the purine salvage enzyme hypoxanthine-guanine-xanthine phosphoribosyltransferase (HGXPRT) to convert purine bases from the host to nucleotides needed for DNA and RNA synthesis. An approach to developing antimalarial drugs is to use HGXPRT to convert introduced purine base analogs to nucleotides that are toxic to the parasite. This strategy requires that these compounds be good substrates for the parasite enzyme but poor substrates for the human counterpart, HGPRT. Bases with a chlorine atom in the 6-position or a nitrogen in the 8-position exhibited strong discrimination between P. falciparum HGXPRT and human HGPRT. The k(cat)/K(m) values for the Plasmodium enzyme using 6-chloroguanine and 8-azaguanine as substrates were 50 - 80-fold and 336-fold higher than for the human enzyme, respectively. These and other bases were effective in inhibiting the growth of the parasite in vitro, giving IC(50) values as low as 1 microM.
Publisher: Oxford University Press (OUP)
Date: 24-05-2013
DOI: 10.1189/JLB.1212653
Abstract: The severity of schistosome egg-induced hepatic granulomatous pathology depends markedly on the nature of the host immune responses. In this study, we used LMM and microarray analysis to compare gene expression profiles of histologically distinct zones within, and directly proximal to, hepatic granulomas that developed in C57BL/6 mice infected with Schistosoma japonicum. There was significant up-regulation of type-1, type-2, and type-17 immune-associated genes within the granuloma core (adjacent to eggs), followed by increased expression of type-2 and fibrotic genes at the outer zones of granulomas. Neutrophil-associated genes were also found to be expressed differentially in the core and at the peripheral zone of granulomas, present at 7 weeks p.i., demonstrating a significant role of neutrophils in S. japonicum granulomatous pathology. The release of NETs was observed microscopically in granulomas obtained from the livers of infected mice and when human neutrophils were incubated in vitro in the presence of S. japonicum eggs. These finding are the first to suggest a novel, dual role for neutrophils in the mediation of tissue damage and repair in S. japonicum egg-induced hepatic granulomatous lesions. Together, these results provide an overview of the local events occurring within the granuloma microenvironment.
Publisher: Elsevier BV
Date: 06-2018
DOI: 10.1016/J.PARINT.2017.12.003
Abstract: Seven species of Psettarium (Digenea: Aporocotylidae), including four new species, are reported from tetraodontiform fishes from off coastal east Queensland. Psettarium pandora n. sp. infects the yellow boxfish, Ostracion cubicus (Ostraciidae), the first known aporocotylid to infect this family of fishes. Three new species are reported from pufferfishes of the genus Arothron (Tetraodontidae): Psettarium yoshidai n. sp. infects the map puffer (Arothron mappa), Psettarium hustoni n. sp. infects the black-spotted puffer (A. nigropunctatus) and Psettarium martini n. sp. infects the starry puffer (A. stellatus). We also report three species of Psettarium from Australian waters for the first time. Paracardicola hawaiensis Martin, 1960, the sole species of Paracardicola, is redescribed based on specimens collected from the type-host, the stars-and-stripes puffer, Arothron hispidus. Paracardicola is synonymised with Psettarium and P. hawaiensis is recombined as Psettarium hawaiiense (Martin, 1960) n. comb. Psettarium pulchellum Yong, Cutmore, Bray, Miller, Semarariana, Palm & Cribb, 2016, described from the narrow-lined puffer (Arothron manilensis) from off Bali, Indonesia, is reported from the same fish species at two locations on the Queensland coast, significantly extending the range of this species. Psettarium nolani (Bray, Cribb & Littlewood, 2013), originally described from French Polynesia, is reported from A. hispidus, A. manilensis and A. stellatus, representing both new host and locality records for this species. Molecular phylogenetic analysis shows these species to all be closely related, such that they cannot be considered to represent separate genera despite their differing morphology. Analysis of 28S sequence data for Psettarium anthicum Bullard & Overstreet, 2006, a non-tetraodontiform-infecting species, shows it to be distantly related to all other species of Psettarium for which sequence data are available. The species is re-assigned to a new genus, Cardallagium n. gen., as Cardallagium anthicum (Bullard & Overstreet, 2006) n. comb. We think it likely that the host range of species of Psettarium is limited to tetraodontiform fishes. We assessed the infection biology of two species, P. nolani and P. hawaiiense n. comb. infecting A. hispidus, using histology to assess the pathways of egg release for these species. Eggs of both species were observed in both circulatory and visceral organs of infected hosts, often in high numbers. Eggs were seen trapped in the mucosal layer of the intestine and, in rare instances, causing lesions in the laminar epithelium, providing the strongest evidence yet that they pass through the gut wall and escape the host via the faeces. Lastly, we discuss the biogeographical implications of our findings, noting that some Psettarium species now show very wide geographical distributions.
Publisher: Elsevier BV
Date: 10-2012
DOI: 10.1016/J.JMB.2012.06.041
Abstract: Alpha-giardins constitute the annexin proteome (group E annexins) in the intestinal protozoan parasite Giardia and, as such, represent the evolutionary oldest eukaryotic annexins. The dominance of alpha-giardins in the cytoskeleton of Giardia with its greatly reduced actin content emphasises the importance of the alpha-giardins for the structural integrity of the parasite, which is particularly critical in the transformation stage between cyst and trophozoite. In this study, we report the crystal structures of the apo- and calcium-bound forms of α1-giardin, a protein localised to the plasma membrane of Giardia trophozoites that has recently been identified as a vaccine target. The calcium-bound crystal structure of α1-giardin revealed the presence of a type III site in the first repeat as known from other annexin structures, as well as a novel calcium binding site situated between repeats I and IV. By means of comparison, the crystal structures of three different alpha-giardins known to date indicate that these proteins engage different calcium coordination schemes, among each other, as well as compared to annexins of groups A-D. Evaluation of the calcium-dependent binding to acidic phosphoplipid membranes revealed that this process is not only mediated but also regulated by the environmental calcium concentration. Uniquely within the large family of annexins, α1-giardin disengages from the phospholipid membrane at high calcium concentrations possibly due to formation of a dimeric species. The observed behaviour is in line with changing calcium levels experienced by the parasite during excystation and may thus provide first insights into the molecular mechanisms underpinning the transformation and survival of the parasite in the host.
Publisher: Springer Science and Business Media LLC
Date: 16-10-2015
DOI: 10.1038/SREP15069
Abstract: Our previously reported gene atlasing of schistosome tissues revealed transcripts that were highly enriched in the digestive tract of Schistosoma mansoni . From these, we selected two candidates, Sm -LAMP and Sm -NPC2 for testing as vaccine targets. The two molecules were selected on the basis of relatively high expression in the gastrodermis, their potentially important biological function, ergence from homologous molecules of the host and possible apical membrane expression in the gastrodermis. Bacterially expressed recombinant peptides corresponding to regions excluding trans-membrane domains of the selected vaccine targets were used in blinded vaccine trials in CBA mice using alum-CpG as adjuvant. Vaccine trials using the recombinant insoluble Sm -LAMP protein showed 16–25% significant reduction in total worm burden. Faecal egg count reduction was 52% and 60% in two trials, respectively, with similar results for the solubly expressed protein. Liver egg burden was reduced significantly (20% and 38%) with an insoluble recombinant Sm -LAMP in two trials, but not with the soluble recombinant form. Parasite fecundity was not affected by either Sm -LAMP protein preparations in the trials. It is concluded that Sm -LAMP may provide limited protection towards S. mansoni infections but could be used in combination with other vaccine candidates, to provide more comprehensive protection.
Publisher: Wiley
Date: 02-2012
DOI: 10.1111/J.1365-3024.2011.01349.X
Abstract: Schistosome research has entered the genomic era with the publications reporting the Schistosoma mansoni and Schistosoma japonicum genomes. Schistosome genomics is motivated by the need for new control tools. However, much can also be learned about the biology of Schistosoma , which is a tractable experimental model. In this article, we review the recent achievements in the field of schistosome research and discuss future perspectives on genomics and how it can be integrated in a usable format, on the genetic mapping and how it has improved the genome assembly and provided new research approaches, on how epigenetics provides interesting insights into the biology of the species and on new functional genomics tools that will contribute to the understanding of the function of genes, many of which are parasite‐ or taxon specific.
Publisher: Wiley
Date: 2004
DOI: 10.1002/BIES.20058
Abstract: Schistosomes are parasitic blood flukes, responsible for significant human disease in tropical and developing nations. Here we review information on the organization of the cytoskeleton and associated motor proteins of schistosomes, with particular reference to the organization of the syncytial tegument, a unique cellular adaptation of these and other neodermatan flatworms. Extensive EST databases show that the molecular constituents of the cytoskeleton and associated molecular systems are likely to be similar to those of other eukaryotes, although there are potentially some molecules unique to schistosomes and platyhelminths. The biology of some components, particular those contributing to host-parasite interactions as well as chemotherapy and immunotherapy are discussed. Unresolved questions in relation to the structure and function of the tegument relate to dynamic organization of the syncytial layer.
Publisher: Public Library of Science (PLoS)
Date: 26-04-2011
Publisher: Public Library of Science (PLoS)
Date: 31-05-2011
Publisher: Elsevier BV
Date: 09-1995
DOI: 10.1016/0020-7519(95)00025-W
Abstract: The ultrastructure and histochemistry of the scolex of a Polypocephalus species is described. This cestode is distinguishable from all known Polypocephalus spp. in that it has approximately 400 tentacles and inhabits the musculature of the blue swimmer crab, Portunus pelagicus. The metacestode has a large scolex, ided into an anterior par apicalis, and a posterior pars basalis. An elongate cercomer lies posteriorly to the scolex. The pars basalis lacks accessory suckers. The tegument of this region is armed with numerous spinous microtiches. The pars apicalis consists of approximately 400 unarmed tentacles, a large cavity ( = scolex cavity) containing some glandular tissue, and lying posteriorly to this cavity, a large gland ( = scolex gland). The tegument of the tentacles and pars apicalis is typically syncytial, and contains abundant electron-opaque secretory vesicles. These vesicles are produced by glandular tissue of the scolex gland and scolex cavity. Histochemistry revealed the presence of proteins and neutral mucosubstances in tentacles, scolex gland and scolex cavity, suggesting the presence of glycoproteins. It is argued that the secretion produced by the tentacles has an adhesive role. When applied to the large interface between the tentacles and the mucosa of the hosts, this secretion may provide the adult parasite with a strong holdfast to prevent dislodgement.
Publisher: Wiley
Date: 06-2009
Publisher: Springer Science and Business Media LLC
Date: 23-07-2011
DOI: 10.1007/S00436-011-2557-3
Abstract: Eggs of most species digenean flukes hatch in the external environment to liberate larvae that seek and penetrate a snail intermediate host. Those of the human liver flukes, Opisthorchis viverrini, hatch within the gastrointestinal canal of their snail hosts. While adult parasites are primarily responsible for the pathology in cases of human opisthorchiasis, their eggs also contribute by inducing granulomata and in serving as nidi for gallstone formation. In view of the peculiar biology of O. viverrini eggs and their contribution to pathology, we investigated embryogenesis in this species by light and transmission electron microscopy. Egg development was traced from earliest stages of coalescence in the ootype until full embryonation in the distal region of the uterus. Fully mature eggs were generally impermeable to resin and could not be examined by conventional electron microscopy methods. However, the use of high-pressure freezing and freeze-substitution fixation of previously fixed eggs enabled the internal structure of mature eggs, particularly the subshell envelopes, to be elucidated. Fertilization occurs in the ootype, and the large zygote is seen therein with a single spermatozoon wrapped around its plasma membrane. As the zygote begins to ide, the spent vitellocytes are pushed to the periphery of the eggs, where they progressively degrade. The early eggshell is formed in the ootype by coalescing eggshell precursor material released by approximately six vitelline cells. The early eggs have a thinner eggshell and are larger than, but lack the characteristic shape of, mature eggs. Characteristic shell ornamentation, the "muskmelon" appearance of eggs, appears after eggshell polymerization in the ootype. Pores are not present in the shell of O. viverrini eggs. The inner and outer envelopes are poorly formed in this species, with the outer envelope evident beneath the eggshell at the opercular pole of the mature egg. The miracidium has a conical anterior end that lacks the distinctive lamellar appearance of the terebratorium of other digeneans, such as the schistosomes. The miracidium is richly glandular, containing an apical gland in the anterior end, large cephalic gland, and posterior secretory glands. Each gland contains a secretory product with different structure. The paucity of vitelline cells associating with eggs, the reduced size of eggs, and reduced complexity of the extraembryonic envelopes are interpreted as adaptations to the peculiar hatching biology of the miracidia.
Publisher: Elsevier BV
Date: 12-1989
Publisher: Elsevier BV
Date: 10-2011
DOI: 10.1016/J.PEP.2011.06.018
Abstract: Granulins (GRNs) are potent growth factors that are upregulated in many aggressive cancers from a wide range of organs. GRNs form tight, disulphide bonded, beta hairpin stacks, making them difficult to express in recombinant form. We recently described Ov-GRN-1, a GRN family member secreted by the carcinogenic liver fluke of humans, Opisthorchis viverrini, and showed that recombinant Ov-GRN-1 expressed and refolded from Escherichia coli caused proliferation of mammalian cell lines at nanomolar concentrations. We now report on an optimized method to express and purify monomeric Ov-GRN-1 in E. coli using a straightforward and scalable purification and refolding process. Purified monomeric protein caused proliferation at nanomolar concentrations of cancerous and non-cancerous cell lines derived from human bile duct tissue. The expression and purification method we describe herein will serve as a backbone upon which to develop expression and purification processes for recombinant GRNs from other organisms, accelerating research on this intriguing family of proteins.
Publisher: Springer Science and Business Media LLC
Date: 19-02-2015
DOI: 10.1007/S00436-015-4369-3
Abstract: The organization and fine structure of the complex copulatory apparatus of Tetrabothrius erostris (Tetrabothriidea) is investigated by light and transmission electron microscopy. A ersity of microstructures was found on the surface of genital ducts. The apical surfaces of male gonadoducts possess tubular and blade-like microtriches that have specific structure in each section of the duct. The apical part of the tubular microtriches contains numerous constrictions in the proximal section of the sperm duct blade-like microtriches of cirrus possess longitudinal striation in the apical part, and their basal part is reinforced with electron-dense strands. Two types of microtriches occur on the surface of cirrus, and their presence may be considered as systematic features. Prostate glands containing granules of medium electron density (up to 130 nm diameter) are localized in the cirrus sac. The genital atrium contains numerous non-ciliated receptors. Paramyosin-like fibers (up to 200 nm) were found in the muscle fibers surrounding the male atrium canal. Microtriches on the surface of the distal region of the male atrial canal are covered by a glycocalyx. Electron-dense, membrane-like structures (up to 40 nm) lie under the apical membrane of the genital atrium and vagina. These structures do not form a continuous layer its edges turn down and sink into the apical invaginations of epithelium. Hypotheses on the possible ways of copulation in T. erostris based on the observed ultrastructure are discussed.
Publisher: Elsevier BV
Date: 11-2018
DOI: 10.1016/J.ACTATROPICA.2018.08.016
Abstract: Ticks (Acari:Ixodoidea) are important ectoparasites infesting livestock and human populations around the globe. Ticks can cause damage directly by affecting the site of infestation, or indirectly as vectors of a wide range of protozoa, bacteria and viruses which ultimately lead to lowered productivity of livestock populations. Hyalomma is a genus of hard ticks, having more than 30 species well-adapted to hot, humid and cold climates. Habitat ersity, vector ability, and emerging problem of acaricidal resistance in enzootic regions typify this genus in various countries around the world. This paper reviews the epidemiology, associated risk factors (temperature, climate, age, sex, breed etc.), vector role, vector-pathogen association, and reported control strategies of genus Hyalomma. The various proteins in saliva of Hyalomma secreted into the blood stream of host and the prolonged attachment are responsible for the successful engorgement of female ticks in spite of host immune defense system. The various immunological approaches that have been tried by researchers in order to cause tick rejection are also discussed. In addition, the novel biological control approaches involving the use of entomo-pathogenic nematodes and Bacillus thuringiensis (B. thuringiensis) serovar thuringiensis H14 an endotoxin, for their acaricidal effect on different species and life cycle stages of Hyalomma are also presented.
Publisher: Wiley
Date: 28-07-2008
DOI: 10.1111/J.1365-3156.2008.02101.X
Abstract: To assess the usefulness of serology as an indicator of Echinococcus transmission for developing preventive measures against echinococcosis in rural communities. Cross-sectional survey in 2002 among 861 children aged 7 to 18 years in Xiji County, Ningxia, China. Before ultrasound abdominal examination, a questionnaire was used to identify socioeconomic, sanitary and hygiene risk factors for echinococcal infection filter paper blood s les were collected from each child for specific antibody detection using EmP (Echinococcus multilocularis) and EgB (Echinococcus granulosus) antigens. Transmission of both E. multilocularis and E. granulosus occur in this area. Serological prevalence was far higher than disease prevalence in this age range. We found no gender-related differences of seroprevalence among the children, suggesting an equal chance of exposure to echinococcal egg-contaminated environments. The seroprevalence distribution was associated with changes in the ecology of wild hosts for E. multilocularis contamination, and with changes in socio-geographic features of the communities for E. granulosus contamination. Serological data obtained for children in mass surveys of echinococcosis appear to be a comprehensive and useful tool to monitor changes of transmission dynamics in humans and provide 'warning signals' to decision makers for the instigation of specific control measures against the disease.
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.EXPPARA.2011.01.002
Abstract: Members of the zinc-regulated transporter/iron-regulated transporter-like protein (ZIP) family of proteins transport metal ions across cell membranes. Genes encoding ZIPs are present in the genomes of schistosomes. Here, we describe molecular characterisation of six ZIPs (SjZIPA-F) from Schistosoma japonicum. Quantitative PCR analyses of these ZIPs through the lifecycle showed that each is expressed predominantly during the intramammalian stage and are particularly enriched in adult females. Using laser microdissected tissue as template, SjZIPA-D were transcriptionally enriched in female reproductive tissues, SjZIPE was not expressed in specific tissues and SjZIPF was expressed similarly in each tissue. Whole mount in situ hybridization revealed that SjZIPA and SjZIPB were localised to the oesophageal gland of adults and the vitellaria. We have shown that multiple ZIPs are expressed by schistosomes during the intramammalian parasitic phases and propose that the encoded products perform erse cellular functions related to metal transport in different cells of S. japonicum.
Publisher: American Society of Parasitologists
Date: 08-2018
DOI: 10.1645/16-125
Abstract: The human liver fluke Opisthorchis viverrini (Platyhelminthes, Trematoda, Digenea) uses snails of the genus Bithynia as first intermediate host. Peculiarly among trematodes, the eggs of O. viverrini hatch within the digestive tract of its snail host. It remains uncertain whether hatching in this species is mediated through mechanical fracture of the eggshell or by digestion with specific digestive enzymes. This study aimed to characterize enzymes with specific inhibitors and factors involved in the hatching activity of O. viverrini eggs. For measuring egg hatching in vivo, 50 O. viverrini mature eggs were fed to in idual Bithynia siamensis goniomphalos snails at various temperature conditions for 24 hr. Ex vivo, mature eggs were incubated with crude snail extract and commercial leucine aminopeptidase (LAP). Egg-hatching of O. viverrini was temperature dependent, with optimal hatching occurring at 24-28 C, with a peak of hatching of 93.54% in vivo and 30.55% ex vivo occurring at these temperatures. Ex vivo hatching rates increased to 45.87% under anaerobic conditions at 28 C. Some 22.70% and 16.21% of heat-killed eggs also hatched within the snail digestive tract and snail extract, respectively, indicating that host molecules are involved in the hatching response. Most eggs hatch in the anterior regions of the digestive tract. Hatching was completely inhibited in the presence of bestatin, an inhibitor of LAP, but not in the presence of phosphatase inhibitors. Bestatin inhibition of hatching was reversible. Finally, egg hatching could be induced by addition of a porcine LAP. The results indicate that this digenean utilizes both LAP of the snail host and movement of miracidia for hatching.
Publisher: Portland Press Ltd.
Date: 12-11-2018
DOI: 10.1042/BST20180480
Abstract: In eukaryotes, effective calcium homeostasis is critical for many key biological processes. There is an added level of complexity in parasites, particularly multicellular helminth worms, which modulate calcium levels while inhabiting the host microenvironment. Parasites ensure efficient calcium homeostasis through gene products, such as the calmodulin-dependent kinases (CaMK), the main focus of this review. The importance of CaMK is becoming increasingly apparent from recent functional studies of helminth and protozoan parasites. Investigations on the molecular regulation of calcium and the role of CaMK are important for both supplementing current drug regimens and finding new antiparasitic compounds. Whereas calcium regulators, including CaMK, are well characterised in mammalian systems, knowledge of their functional properties in parasites is increasing but is still in its infancy.
Publisher: FapUNIFESP (SciELO)
Date: 09-2017
DOI: 10.1590/0037-8682-0040-2017
Abstract: Immunogenicity of Schistosoma mansoni egg surface was examined to determine whether intact eggshells have lower antigenicity than ruptured eggs. Swiss Webster mice were inoculated with intact or ultrasonicated S. mansoni eggs isolated from infected human feces. Mice were separated into four groups of six animals each and immunizations were performed approximately every 20 days during a 60-day period. Groups 1-4 were administered with saline solution, sonicated eggs with Freund's adjuvant, sonicated eggs without Freund's adjuvant, and intact eggs, respectively. IgG humoral immune response was assessed by ELISA using Soluble Egg Antigen produced from eggs isolated from the livers of infected mice. Sonicated eggs co-administered with adjuvant induced the highest humoral response at 58 days, which was 11.9-fold (95% CI 6.2-17.5) greater than the response induced by saline solution. Sonicated eggs without adjuvant induced a 4.3-fold stronger response (95% CI 2.4-6.2) than normal saline. Intact eggs induced humoral response that was nominally twice stronger (95% CI 0.8-3.2) than that induced by normal saline but the effect did not reach statistical significance. Soluble antigens are not abundant on the surface of S. mansoni eggs and/or are not secreted in sufficient quantities to induce a significant immune response to intact eggs. Assuming that isolation procedures had not damaged the eggs used for inoculation, our observations suggest that intact eggs either do not induce a significant immune response or, if they do, the mechanism involves insoluble antigens from the egg surface.
Publisher: Wiley
Date: 2002
DOI: 10.1111/J.1751-0813.2002.TB12831.X
Abstract: A 12-day-old nestling Gouldian finch (Erythrura [Chloebia] gouldiae) was presented for investigation of a mortality problem in nestling finches raised by Bengalese finch foster parents. On histological examination, large numbers of spores consistent with a microsporidian organism were present within the small intestinal mucosa. Electron microscopy and molecular studies (sequencing the 5' end of the ssu rRNA gene) further defined the organism as Encephalitozoon hellem. Sequence homology with other eukaryotes was determined using a BLASTN search from the NCBI GenBank database. The finch isolate sequences showed greater than 99% homology with those of previously reported human and avian isolates.
Publisher: Elsevier BV
Date: 06-1996
Abstract: Although many workers have investigated the maturation and processing of the flavivirus nonstructural glycoprotein NS1 in infected cells, these studies have provided little insight into a possible function for NS1. In this study we investigated the subcellular localization of NS1 both by immunofluorescence and cryo-immuno electron microscopy of infected Vero and C6/36 cells. NS1 was found to be tightly associated with intracellular membranes, in particular with vesicle packets and large cytoplasmic vacuoles. Surprisingly, NS1 did not associate with mature virus particles, a finding that is inconsistent with the postulated role for this protein in virion assembly and/or maturation. However, dual-labeling experiments did reveal in both the confocal immunofluorescence and cryo-immuno EM studies the colocalization of NS1 with the viral dsRNA replicative form. Furthermore, localization of the dsRNA to the vesicle packets and cytoplasmic vacuoles seen in infected Vero and C6/36 cells, respectively, suggests that these structures may comprise the flavivirus replication complex. These findings provide further insights into the maturation pathway of NS1 and suggest a possible role for this protein in viral RNA replication.
Publisher: Cold Spring Harbor Laboratory
Date: 09-07-2020
DOI: 10.1101/2020.07.08.190694
Abstract: CRISPR/Cas9-mediated genome editing shows cogent potential for the genetic modification of helminth parasites. Here we report successful gene knock-in (KI) into the genome of the egg of Schistosoma mansoni by combining CRISPR/Cas9 with single-stranded oligodeoxynucleotides (ssODNs). We edited the acetylcholinesterase (AChE) gene of S. mansoni targeting two guide RNAs (gRNAs), X5 and X7, located on exon 5 and exon 7 of Smp_154600, respectively. A CRISPR/Cas9-vector encoding gRNA X5 or X7 was introduced by electroporation into eggs recovered from livers of experimentally infected mice. Simultaneously, eggs were transfected with a ssODN donor encoding a stop codon in all six frames, flanked by 50 nt-long 5’- and 3’-homology arms matching the predicted Cas9-catalyzed double stranded break at X5 or X7. Next generation sequencing analysis of reads of licon libraries spanning targeted regions revealed that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). Furthermore, soluble egg antigen from AChE-edited eggs exhibited markedly reduced AChE activity, indicative that programmed Cas9 cleavage mutated the AChE gene. Following injection of AChE-edited schistosome eggs into the tail veins of mice, a significant decrease in circumoval granuloma size was observed in the lungs of the mice. Notably, there was an enhanced Th2 response involving IL-4, −5, −10, and-13 induced by lung cells and splenocytes in mice injected with X5-KI eggs in comparison to control mice injected with unmutated eggs. A Th2-predominant response, with increased levels of IL-4, −13 and GATA3, also was induced by X5 KI eggs in small intestine-draining mesenteric lymph node cells when the gene-edited eggs were introduced into the subserosa of the ileum of the mice. These findings confirmed the potential and the utility of CRISPR/Cas9-mediated genome editing for functional genomics in schistosomes. Schistosomiasis is the most devastating of the parasitic helminth diseases. Currently, no vaccines are available for human use and praziquantel is the only available treatment raising considerable concern that drug resistance will develop. A major challenge faced by the schistosomiasis research community is the lack of suitable tools to effectively characterise schistosome gene products as potential new drug and/or vaccine targets. We introduced CRISPR/Cas9 mediated editing into S. mansoni eggs targeting the gene encoding acetylcholinesterase (AChE), a recognized anthelminthic drug target. We found that the major modifications induced by CRISPR/Cas9 in the eggs were generated by homology directed repair (HDR). This platform provides a unique opportunity to generate precise loss-of-function insertions into the schistosome genome. We pre-screened the activity of two guide RNAs of the AChE gene and compared/validated the mutation efficacy using next-generation sequencing analysis at the genomic level and phenotypic modifications at the protein level. That resulted in reduced AChE activity observed in AChE-edited eggs, and decreased lung circumoval granuloma size in mice injected with those edited eggs. The CRISPR/Cas9-genome editing system we established in this study provides a pivotal platform for gene functional studies to identify and test new anti-schistosome intervention targets, which can be extended to the other human schistosome species and other important parasitic helminths.
Publisher: Elsevier BV
Date: 04-2018
Abstract: To date, reliable techniques that can provide accurate information on the local and global prevalence of schistosomiasis are still associated with high costs or labour-intensive processes. Here we discuss old and new concepts for diagnostic approaches, and we highlight structural properties of schistosome eggshells that result in their affinity for magnetic materials as a new diagnostic approach.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.IJPARA.2005.09.001
Abstract: The signal sequence trap technique was applied to identify genes coding for secreted and membrane bound proteins from Echinococcus granulosus, the etiologic agent of cystic hydatid disease. An E. granulosus protoscolex cDNA library was constructed in the AP-PST vector such that randomly primed cDNAs were fused with a placental alkaline phosphatase reporter gene lacking its endogenous signal peptide. E. granulosus cDNAs encoding a functional signal peptide were selected by their ability to rescue secretion of alkaline phosphatase by COS-7 cells that had been transfected with the cDNA library. Eighteen positive clones were identified and sequenced. Their deduced amino acid sequences showed significant similarity with amino acid transporters, Krebs cycle intermediates transporters, presenilins and vacuolar protein sorter proteins. Other cDNAs encoded secreted proteins without homologues. Three sequences were transcribed antisense to E. granulosus expressed sequence tags. All the mRNAs were expressed in protoscoleces and adult worms, but some of them were not found in oncospheres. The putative E. granulosus secreted and membrane bound proteins identified are likely to play important roles in the metabolism, development and survival in the host and represent potential targets for diagnosis, drugs and vaccines against E. granulosus.
Publisher: Elsevier BV
Date: 12-2021
Publisher: Cambridge University Press (CUP)
Date: 02-1997
DOI: 10.1017/S003118209600830X
Abstract: Based on substrate preferences, cercariae of Schistosoma mansoni were seen to express both cathepsin L and cathepsin B cysteine proteinases, although the former activity was many -fold greater. Two cathepsin L activities identified in cercarial extracts by zymography co-migrated with activities in extracts of 3 h and 24 h schisotosomula and in extracts of adult worms. Since these enzymes have been implicated in haemoglob in digestion by adult worms, they may perform a similar function in schistosomula. Immunolocalization using scanning electron micrographs showed that cathepsin L and cathepsin B proteinases were present in the cercarial post-acetabular glands. In addition, cercarial serine proteinase activities considered to facilitate skin penetration efficiently cleaved the substrates Z-Gly-Pro-Arg-NHMec and Z-Gly-Pro-Lys-NHMec. Cercariae release most of this serine proteinase activity when induced to secrete the contents of their acetabular glands. In contrast, newly transformed 3 h and 24 h schistosomula did not express this activity.
Publisher: Elsevier BV
Date: 06-1999
DOI: 10.1016/S0167-4838(99)00089-8
Abstract: Dynein light chains (DLC) are components of dynein, an enzyme complex involved in various aspects of microtubule-based motility. We report here the molecular cloning and sequencing of cDNAs encoding a family of DLC-like polypeptides (SjcDLC1-5) from the human bloodfluke Schistosoma japonicum with open reading frames of 87-104 amino acids and deduced molecular masses ranging from 10.5 to 12.3 kDa. Two-dimensional Western blot analysis confirmed the presence of several S. japonicum DLC isoforms with differing pI values and molecular sizes. We also describe the molecular characterisation, genomic organisation and expression of clone SjcDLC1, and the immunological characterisation and localisation of its encoded protein. Northern blot analysis of adult worm RNA indicated SjcDLC1 is encoded by a single message of approximately 650 bp and Southern analysis suggested one SjcDLC1 gene exists in the S. japonicum genome. Immunolocalisation studies demonstrated that the SjcDLC1 protein is present in the tegument of the adult and cercarial stages of S. japonicum. SjcDLC1 and the other SjcDLC may function in the transport of specialised organelles, comprising membranous and discoid bodies, through the tegument to the schistosome-unique heptalaminate tegumental membrane at the external surface of the adult worm. As a consequence, they may provide novel targets for anti-schistosome vaccine and/or drug development.
Publisher: Elsevier BV
Date: 1999
DOI: 10.1016/S0166-6851(98)00171-6
Abstract: The gene for a Schistosoma japonicum (Philippine strain origin) (Sjp) calponin-like protein has been cloned and characterised. The clone, designated P14, was isolated from a Sjp adult worm lambda ZAP cDNA library by immunoscreening, and was shown to contain a full-length cDNA encoding a 38.3 kDa protein that shared significant sequence similarity to a number of previously reported calponins and 22 kDa smooth-muscle proteins. Northern analysis indicated the P14 transcript was approximately 2.2 kb in both Sjp and Chinese strain S. japonicum (Sjc) adult worms. Southern blot analysis of genomic DNA suggested that several copies of the P14 gene are present in the Sjc and Sjp genomes but only one copy was evident in the S. mansoni (Sm) genome. Western blot analysis indicated that the product of P14 occurs as a 38 kDa protein in adult Sjp worms and homologues are present in adult worms of Sjc and Sm. At least six isoforms, all with a similar molecular size of approximately 38 kDa and isoelectric points ranging from 8.1 to 9.5, were present in adult Sjc worms. The protein was immunolocalized to the muscle of male and female Sjc adult worms. Recombinant protein was expressed in E. coli and purified under denaturing conditions, and in yeast to produce a soluble protein in purified form. The availability of purified, correctly folded protein will allow investigations into its biological functions and potential involvement in host immunity.
Publisher: Cambridge University Press (CUP)
Date: 06-05-2019
DOI: 10.1017/S0031182019000465
Abstract: The investigation of the glycan repertoire of several organisms has revealed a wide variation in terms of structures and abundance of glycan moieties. Among the parasites, it is possible to observe different sets of glycoconjugates across taxa and developmental stages within a species. The presence of distinct glycoconjugates throughout the life cycle of a parasite could relate to the ability of that organism to adapt and survive in different hosts and environments. Carbohydrates on the surface, and in excretory-secretory products of parasites, play essential roles in host–parasite interactions. Carbohydrate portions of complex molecules of parasites stimulate and modulate host immune responses, mainly through interactions with specific receptors on the surface of dendritic cells, leading to the generation of a pattern of response that may benefit parasite survival. Available data reviewed here also show the frequent aspect of parasite immunomodulation of mammalian responses through specific glycan interactions, which ultimately makes these molecules promising in the fields of diagnostics and vaccinology.
Publisher: Elsevier BV
Date: 06-2020
Publisher: Elsevier BV
Date: 06-2020
Publisher: Springer Science and Business Media LLC
Date: 26-06-2012
DOI: 10.1007/S00436-012-2990-Y
Abstract: Adult specimens of Skrjabinacanthus diplocoronatus and Urocystis prolifer were investigated by light and transmission electron microscopy, and data on the uterine organization in these species are presented. The interrelationships of morphological changes of the uterus and developing eggs on the one hand with fecundities of the strobilae of cyclophyllidean cestodes on the other hand are investigated. The development of the excretory system forming a network of excretory ducts close to the uterus is characteristic of S. diplocoronatus. Numerous excretory ducts are located near the uterus or contact the uterine epithelium and are also found in uterine cords. Accumulation of lipids is observed in the cavity of excretory ducts, in muscular cells, and in the lumen of the uterus as well as in the developing eggs. This species displays the largest fecundity among cestode parasites of the shrew. U. prolifer has one of the lowest fecundities among cestodes from shrews. A small amount of lipids found in cells of gravid proglottids could serve as a supply of nutrients. It seems that some cestodes with great fecundity possess specific paths by which eggs are supplied with nutrients. As a result, erse modifications of the uterus in Cyclophyllidea are formed.
Publisher: Proceedings of the National Academy of Sciences
Date: 20-06-2011
Abstract: Plasmodium spp. parasites cause malaria in 300 to 500 million in iduals each year. Disease occurs during the blood-stage of the parasite's life cycle, where the parasite is thought to replicate exclusively within erythrocytes. Infected in iduals can also suffer relapses after several years, from Plasmodium vivax and Plasmodium ovale surviving in hepatocytes. Plasmodium falciparum and Plasmodium malariae can also persist after the original bout of infection has apparently cleared in the blood, suggesting that host cells other than erythrocytes (but not hepatocytes) may harbor these blood-stage parasites, thereby assisting their escape from host immunity. Using blood stage transgenic Plasmodium berghei -expressing GFP (PbGFP) to track parasites in host cells, we found that the parasite had a tropism for CD317 + dendritic cells. Other studies using confocal microscopy, in vitro cultures, and cell transfer studies showed that blood-stage parasites could infect, survive, and replicate within CD317 + dendritic cells, and that small numbers of these cells released parasites infectious for erythrocytes in vivo. These data have identified a unique survival strategy for blood-stage Plasmodium , which has significant implications for understanding the escape of Plasmodium spp. from immune-surveillance and for vaccine development.
Publisher: Cambridge University Press (CUP)
Date: 03-08-2020
DOI: 10.1017/S0031182020001250
Abstract: Praziquantel (PZQ) is the drug of choice for schistosomiasis. The potential drug resistance necessitates the search for adjunct or alternative therapies to PZQ. Previous functional genomics has shown that RNAi inhibition of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) gene in Schistosoma adult worms significantly improved the effectiveness of PZQ. Here we tested the in vitro efficacy of 15 selective and non-selective CaMK inhibitors against Schistosoma mansoni and showed that PZQ efficacy was improved against refractory juvenile parasites when combined with these CaMK inhibitors. By measuring CaMK activity and the mobility of adult S. mansoni , we identified two non-selective CaMK inhibitors, Staurosporine (STSP) and 1Naphthyl PP1 (1NAPP1), as promising candidates for further study. The impact of STSP and 1NAPP1 was investigated in mice infected with S. mansoni in the presence or absence of a sub-lethal dose of PZQ against 2- and 7-day-old schistosomula and adults. Treatment with STSP/PZQ induced a significant (47–68%) liver egg burden reduction compared with mice treated with PZQ alone. The findings indicate that the combination of STSP and PZQ dosages significantly improved anti-schistosomal activity compared to PZQ alone, demonstrating the potential of selective and non-selective CaMK/kinase inhibitors as a combination therapy with PZQ in treating schistosomiasis.
Publisher: Wiley
Date: 10-03-2009
DOI: 10.1111/J.1365-3024.2009.01098.X
Abstract: Schistosomiasis continues to be a significant cause of parasitic morbidity and mortality worldwide. This review considers the basic features of the pathology and clinical outcomes of hepatointestinal and genitourinary schistosomiasis, presents an overview of the numerous studies on animal models that have clarified many of the immunopathological features, and provides insight into our current understanding of the immunopathogenesis and genetic control of human schistosomiasis. In murine schistosomiasis, pathology is induced by a CD4(+) Th2 driven granulomatous response directed against schistosome eggs lodged in the host liver. The Th2 cytokines IL-4 and IL-13 drive this response, whereas IL-10, IL13Ralpha2, IFN-gamma and a subset of regulatory T-cells act to limit schistosome induced pathology. A variety of cell types including hepatic stellate cells, alternatively activated macrophages and regulatory T-cells have also been implicated in the pathogenesis of schistosomiasis. Current knowledge suggests the immunopathogenic mechanisms underlying human schistosomiasis are likely to be similar. The review also considers the future development of anti-pathology schistosome vaccines. As fibrosis is an important feature of many other diseases such as Crohn's disease and sarcoidosis, a comprehensive understanding of the cellular and molecular mechanisms involved in schistosomiasis may also ultimately contribute to the development an effective disease intervention strategy for other granulofibrotic diseases.
Publisher: Cambridge University Press (CUP)
Date: 09-1996
DOI: 10.1017/S0031182000081993
Abstract: Murine monoclonal and polyclonal antisera, raised against the 38 kDa subunit of Echinococcus granulosus antigen 5, were used to investigate the tissue distribution of the antigen in hydatid cysts. Immunoreactivity was visualized by indirect immunofluorescence on whole protoscoleces, and ultrastructural immunocytochemistry utilizing colloidal gold-based labelling procedures on unsectioned and cryosectioned brood capsules and protoscoleces. In protoscoleces, the 38 kDa subunit of antigen 5 was localized at the interface of parenchymal cells and associated extracellular matrices, as well as along the interface of the tegumentary syncytium in the somal region and its basal matrix. Cytoplasmic labelling of parenchymal cells was rare when observed, it was associated with vesicles and membranes in cytoplasmic extensions of parenchymal cells. In brood capsules, the antigen was associated with the external face of the plasma of degenerating parenchymal cells. The 38 kDa subunit occurs along the extracellular face of cell membranes, suggesting that antigen 5 is either a component of the membranes or associated extracellular matrices.
Publisher: Springer Science and Business Media LLC
Date: 21-03-2016
DOI: 10.1007/S00436-016-4997-2
Abstract: Some cyclophyllidean cestodes provide protection for their eggs in the external environment by providing them with additional protective layers around the egg membranes. In attempting to examine such adaptations, the microanatomy and fine structure of the uterus of pregravid and gravid proglottids of the cyclophyllidean cestode Orthoskrjabinia junlanae, a parasite of mammals that inhabit a terrestrial but moist environment, were studied. In the initial stages of uterine development, developing embryos locate freely in the lumen of a saccate uterus that later partitions into chambers. Each chamber that forms encloses several embryos. The chambers are surrounded by muscle cells that synthesize extracellular matrix actively. The paruterine organs consist of stacks of flattened long outgrowths of muscular cells, interspersed with small lipid droplets. In the gravid proglottids, the size of paruterine organ increases and consists of flattened basal and small rounded apical parts separated by constrictions. The fine structure of the organ wall remains the same: sparse nuclei and stacks of flattened cytoplasmic outgrowths but internal invaginations or lumen in the paruterine organ are absent. Completely developed eggs remain localized in the uterus. Based on the comparative morpho-functional analysis of uterine and paruterine organs and uterine capsules in cestodes, we conclude that these non-functioning paruterine organ in O. junlanae is an ex le of an atavism. We postulate that the life cycle of the parasite, which infects mammals living in wet habitats, where threats of desiccation of parasite ova is reduced, has favoured a reversion to a more ancestral form of uterine development.
Publisher: Elsevier BV
Date: 11-2019
Abstract: Scabies is a common skin disease with an estimated worldwide incidence of 200 million people infected per year. Its morbidity and mortality is principally due to secondary bacterial infections, a link now well recognized and prompting the recent inclusion of this disease-complex in the WHO list of neglected tropical diseases. The few treatments available are poorly effective against Sarcoptes scabiei eggs and appear to induce resistance in the parasite. An ideal alternative would be a single-dose regimen that kills all developmental stages, including eggs. Drugs used in the veterinary field and applied to other arthropods could be tested experimentally in an established pig-scabies model. Moreover, functional genomics combined with target validation through biochemical research should assist in identifying new drugs.
Publisher: Public Library of Science (PLoS)
Date: 16-11-2010
Publisher: Elsevier BV
Date: 12-2020
Publisher: Wiley
Date: 26-02-2010
Publisher: Wiley
Date: 2001
DOI: 10.1002/CNE.1164
Abstract: The nervous system of temnocephalid flatworms consists of the brain and three pairs of longitudinal connectives extending into the trunk and tail. The connectives are crosslinked by an invariant number of regularly spaced commissures. Branches of the connectives innervate the tentacles of the head and the sucker organ in the tail. A set of nerve rings encircling the pharynx and connected to the brain and connectives constitute the pharyngeal nervous system. The nervous system is formed during early embryogenesis when the embryo represents a multilayered mesenchymal mass of cells. Gastrulation and the formation of separate epithelial germ layers that characterize most other animal groups are absent. The brain arises as a bilaterally symmetric condensation of postmitotic cells in the deep layers of the anterior region of the embryonic mesenchyme. The pattern of axon outgrowth, visualized by labeling with anti-acetylated tubulin (acTub) antibody, shows marked differences from the pattern observed in other flatworm taxa in regard to the number of neurons that express the acTub epitope. Acetylated tubulin is only expressed in neurons that form long axon tracts. In other flatworm species, such as the typhloplanoid Mesostoma and the polyclad Imogine, which were investigated by us with the acTub antibody (Hartenstein and Ehlers [2000] Dev. Genes Evol. 210:399-415 Younossi-Hartenstein and Hartenstein [2000] Dev. Genes Evol. 210:383-398), only a small number of "pioneer neurons" become acTub positive during the embryonic period. By contrast, in temnocephalids, most, if not all, neurons express acTub and form long, large-diameter axons. Initially, the brain commissure, pharyngeal nerve ring, and the connectives are laid down. Commissural tracts and tentacle nerves branching off the connectives appear later. We speculate that the precocious differentiation of the nervous system may be related to the fact that temnocephalids move by muscle action, and possess a massive and complex muscular system when they hatch. In addition, they have muscular specializations such as the anterior tentacles and the posterior sucker that are used as soon as they hatch. By contrast, juveniles of Mesostoma and larvae of polyclads move predominantly by ciliary action that may not require a complex neural circuitry for coordination.
Publisher: Springer Science and Business Media LLC
Date: 11-10-2013
DOI: 10.1038/SREP02893
Publisher: American Society of Tropical Medicine and Hygiene
Date: 06-2008
Publisher: Biology Centre, AS CR
Date: 12-2000
DOI: 10.14411/FP.2000.050
Abstract: The tetraphyllidean metacestode ersity of 310 teleost fishes, including 87 species from 31 families, was examined from Heron Island, The Great Barrier Reef, Australia. Eleven metacestode 'types' were identified with the use of light microscopy. Host-specificity varied greatly among metacestode types. Incorporation of in vitro cultivation allowed generic identification for some types. Types 1 and 2 belong to Uncibilocularis Southwell, 1925, and have triloculate bothridia and one pair of forked hooks with unequal prongs Type 3 has quadriloculate bothridia. Hook development was insufficient to determine in which genus, Acanthobothrium van Beneden, 1849 or Calliobothrium van Beneden, 1850, this type may belong. Type 4 has unilocular bothridia with simple edges and belongs to Anthobothrium van Beneden, 1850. Type 5 has multiloculated bothridia which are invaginated within pouches. This type belongs to the Rhinebothriinae although its generic identity cannot be determined. The bothridia of Type 5 everted within 24 hours of in vitro cultivation and revealed the presence of two forms, one having 48 loculi per bothridium, the other 72 per bothridium. In vitro studies provide additional support for existing theories of onchobothriid scolex development.
Start Date: 2010
End Date: 12-2013
Amount: $225,000.00
Funder: Australian Research Council
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