ORCID Profile
0000-0002-4392-3863
Current Organisation
Monash University
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Publisher: Oxford University Press (OUP)
Date: 12-06-2020
Abstract: Staphylococcus aureus causes necrotizing pneumonia by secreting toxins such as leukocidins that target front-line immune cells. The mechanism by which leukocidins kill innate immune cells and trigger inflammation during S. aureus lung infection, however, remains unresolved. Here, we explored human-induced pluripotent stem cell-derived macrophages (hiPSC-dMs) to study the interaction of the leukocidins Panton–Valentine leukocidin (PVL) and LukAB with lung macrophages, which are the initial leukocidin targets during S. aureus lung invasion. hiPSC-dMs were susceptible to the leukocidins PVL and LukAB and both leukocidins triggered NLPR3 inflammasome activation resulting in IL-1β secretion. hiPSC-dM cell death after LukAB exposure, however, was only temporarily dependent of NLRP3, although NLRP3 triggered marked cell death after PVL treatment. CRISPR/Cas9-mediated deletion of the PVL receptor, C5aR1, protected hiPSC-dMs from PVL cytotoxicity, despite the expression of other leukocidin receptors, such as CD45. PVL-deficient S. aureus had reduced ability to induce lung IL-1β levels in human C5aR1 knock-in mice. Unexpectedly, inhibiting NLRP3 activity resulted in increased wild-type S. aureus lung burdens. Our findings suggest that NLRP3 induces macrophage death and IL-1β secretion after PVL exposure and controls S. aureus lung burdens.
Publisher: Life Science Alliance, LLC
Date: 28-03-2023
Abstract: Staphylococcus aureus causes severe infections such as pneumonia and sepsis depending on the pore-forming toxin Panton–Valentine leukocidin (PVL). PVL kills and induces inflammation in macrophages and other myeloid cells by interacting with the human cell surface receptor, complement 5a receptor 1 (C5aR1). C5aR1 expression is tighly regulated and may thus modulate PVL activity, although the mechanisms involved remain incompletely understood. Here, we used a genome-wide CRISPR/Cas9 screen and identified F-box protein 11 (FBXO11), an E3 ubiquitin ligase complex member, to promote PVL toxicity. Genetic deletion of FBXO11 reduced the expression of C5aR1 at the mRNA level, whereas ectopic expression of C5aR1 in FBXO11 −/− macrophages, or priming with LPS, restored C5aR1 expression and thereby PVL toxicity. In addition to promoting PVL-mediated killing, FBXO11 d ens secretion of IL-1β after NLRP3 activation in response to bacterial toxins by reducing mRNA levels in a BCL-6–dependent and BCL-6–independent manner. Overall, these findings highlight that FBXO11 regulates C5aR1 and IL-1β expression and controls macrophage cell death and inflammation following PVL exposure.
Publisher: Springer Science and Business Media LLC
Date: 17-01-2022
DOI: 10.1038/S41467-022-28012-5
Abstract: A depleted antimicrobial drug pipeline combined with an increasing prevalence of Gram-negative ‘superbugs’ has increased interest in nano therapies to treat antibiotic resistance. As cubosomes and polymyxins disrupt the outer membrane of Gram-negative bacteria via different mechanisms, we herein examine the antimicrobial activity of polymyxin-loaded cubosomes and explore an alternative strategy via the polytherapy treatment of pathogens with cubosomes in combination with polymyxin. The polytherapy treatment substantially increases antimicrobial activity compared to polymyxin B-loaded cubosomes or polymyxin and cubosomes alone. Confocal microscopy and neutron reflectometry suggest the superior polytherapy activity is achieved via a two-step process. Firstly, electrostatic interactions between polymyxin and lipid A initially destabilize the outer membrane. Subsequently, an influx of cubosomes results in further membrane disruption via a lipid exchange process. These findings demonstrate that nanoparticle-based polytherapy treatments may potentially serve as improved alternatives to the conventional use of drug-loaded lipid nanoparticles for the treatment of “superbugs”.
An updated and annotated checklist of the Dolichodoridae
(Nematoda: Tylenchoidea) of Iran
Publisher: Magnolia Press
Date: 31-03-2014
DOI: 10.11646/ZOOTAXA.3784.4.5
Abstract: The list of plant parasitic nematodes of the family Dolichodoridae, known from Iran, is updated. 81 species belonging to 13 genera and three subfamilies are included in the list. Data for 29 species are added, of which seven species viz. Neodolichorhynchus phaseoli, Pratylenchoides crenicauda, P. erzurumensis, P. utahensis, Scutylenchus paniculoides, Trophurus impar and Tylenchorhynchus variannus are new records for the Iranian nematofauna. The list of species, further information on their morphometrics, references, referring to full or partial descriptions, associated plants, geographical distribution and some taxonomic remarks are provided. More detailed studies on some doubtful populations are proposed. The information on the taxonomic position of species in different classification schemes, as well as, the tendency of the species to certain climatic condition or ecological niche are provided. Challenges on the reliable identification of this group of nematodes in Iran are discussed and finally, suggestions were proposed for future studies.
Publisher: Springer Science and Business Media LLC
Date: 24-02-2016
DOI: 10.1038/NMICROBIOL.2015.34
Abstract: Human pathogenic Legionella replicate in alveolar macrophages and cause a potentially lethal form of pneumonia known as Legionnaires' disease(1). Here, we have identified a host-directed therapeutic approach to eliminate intracellular Legionella infections. We demonstrate that the genetic deletion, or pharmacological inhibition, of the host cell pro-survival protein BCL-XL induces intrinsic apoptosis of macrophages infected with virulent Legionella strains, thereby abrogating Legionella replication. BCL-XL is essential for the survival of Legionella-infected macrophages due to bacterial inhibition of host-cell protein synthesis, resulting in reduced levels of the short-lived, related BCL-2 pro-survival family member, MCL-1. Consequently, a single dose of a BCL-XL-targeted BH3-mimetic therapy, or myeloid cell-restricted deletion of BCL-XL, limits Legionella replication and prevents lethal lung infections in mice. These results indicate that repurposing BH3-mimetic compounds, originally developed to induce cancer cell apoptosis, may have efficacy in treating Legionnaires' and other diseases caused by intracellular microbes.
Publisher: Magnolia Press
Date: 09-12-2016
DOI: 10.11646/ZOOTAXA.4205.5.4
Abstract: Some nematologists recently placed the genus Pratylenchoides, (“Lesion Nematode-like”) in the family Merliniidae. To investigate Pratylenchoides species ersity and their relationships with other Merliniidae genera, specimens were collected from various habitats in the northern and northwestern provinces of Iran. The morphological and molecular study yielded three species of the genus Pratylenchoides, including P. persicus n. sp. This new species is characterized by having lip region rounded or slightly flattened anteriorly with four or five fine but distinct annuli, pharyngeal glands off-set or slightly overlapping the intestine dorsally, all three gland nuclei located anterior to the pharyngo-intestinal valve and tail cylindrical with truncate to low rounded terminus. Morphologically, P. persicus n. sp. can be distinguished from the most closely related species, P. heathi by having shorter body and stylet length in females and males, as well as a shorter tail with different terminus in females. Pratylenchoides laticauda and P. cf. nevadensis are reported from Iran for the first time. Phylogenetic analysis based on the D2/D3 region of the large subunit of ribosomal DNA revealed Pratylenchoides as a monophyletic genus, and it supports the delineation of the new species, P. persicus n. sp.
Publisher: Elsevier BV
Date: 05-2021
Publisher: Hindawi Limited
Date: 22-02-2016
DOI: 10.1111/CMI.12573
Abstract: Macrophages can respond to microbial infections with programmed cell death. The major cell death pathways of apoptosis, pyroptosis and necroptosis are tightly regulated to ensure adequate immune reactions to virulent and persistent invaders. Macrophage death eliminates the replicative niche of intracellular pathogens and induces immune attack. Not surprisingly, successful pathogens have evolved strategies to modulate macrophage cell death pathways to enable microbial survival and replication. Uncontrolled macrophage death can also lead to tissue damage, which may augment bacterial dissemination and pathology. In this review, we highlight how pathogens hijack macrophage cell death signals to promote microbial survival and immune evasion.
Publisher: American Chemical Society (ACS)
Date: 11-12-2017
DOI: 10.1021/ACSCHEMBIO.7B00836
Abstract: Polymyxins are last-line antibiotics against life-threatening multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance is increasingly reported, leaving a total lack of therapies. Using lipidomics and transcriptomics, we discovered that polymyxin B induced lipid A deacylation via pagL in both polymyxin-resistant and -susceptible Pseudomonas aeruginosa. Our results demonstrated that the deacylation of lipid A is an "innate immunity" response to polymyxins and a key compensatory mechanism to the aminoarabinose modification to confer high-level polymyxin resistance in P. aeruginosa. Furthermore, cutting-edge neutron reflectometry studies revealed that an assembled outer membrane (OM) with the less hydrophobic penta-acylated lipid A decreased polymyxin B penetration, compared to the hexa-acylated form. Polymyxin analogues with enhanced hydrophobicity displayed superior penetration into the tail regions of the penta-acylated lipid A OM. Our findings reveal a previously undiscovered mechanism of polymyxin resistance, wherein polymyxin-induced lipid A remodeling affects the OM packing and hydrophobicity, perturbs polymyxin penetration, and thereby confers high-level resistance.
Publisher: Public Library of Science (PLoS)
Date: 06-10-2016
Publisher: American Chemical Society (ACS)
Date: 11-08-2022
Abstract: Nitric oxide (NO)-releasing nanoparticles are effective nanomedicines with erse therapeutic advantages compared with small molecule-based NO donors. Here, we report a new class of furoxan-based NO-releasing nanoparticles using a simple, creative yet facile coassembly approach. This is the first time we demonstrated that the coassembled NO-releasing nanoparticles with poly(ethylene glycol)
Publisher: Magnolia Press
Date: 09-01-2017
DOI: 10.11646/ZOOTAXA.4216.4.4
Abstract: Ditylenchus sturhani sp. n. from the rhizosphere of grasses in East Azarbaijan province, Northwestern Iran, is described and illustrated. The new species is characterised by a straight to slightly arcuate body 656-865 µm in length, presence of four incisures in each lateral field, slender stylet 10–12 µm in length, pharyngeal basal bulb offset or slightly overlapping the intestine, post-uterine sac 1.0–1.9 vulval body diameter long and conical tail with finely rounded terminus. Differences with closely related species including D. solani, D. ausafi, D. angustus, D. dipsaci, D. drepanocercus, D. obesus and D. gallaeformans are discussed. In addition, Iranian populations of two known species, D. valveus and D. virtudesae, are morphologically characterised.
Publisher: Magnolia Press
Date: 04-08-2017
DOI: 10.11646/ZOOTAXA.4300.4.6
Abstract: Comparative morphology of the anterior end is used to characterise certain genera and species of the family Merliniidae, based on populations of 18 species collected from different localities in Iran. We discuss the importance of anterior end morphology in separating Pratylenchoides from Amplimerlinius, and Paramerlinius from Merlinius and Nagelus, as well as for identifying species in the genera Amplimerlinius, Merlinius and Geocenamus. Furthermore, descriptions, morphometric data, line drawings and photomicrographs are provided for Pratylenchoides leiocauda and Telotylenchus paaloofi as new records for the Iranian nematode fauna. Finally, updated species identification keys for the genera Macrotylenchus, Merlinius, Nagelus and Paramerlinius are given.
Publisher: Brill
Date: 2016
DOI: 10.1163/15685411-00003023
Abstract: The genus Pratylenchoides has recently been transferred from the family Pratylenchidae to Merliniidae. To investigate further the relationship between these ‘ Pratylenchus -like’ species (residing in the subfamily Pratylenchoidinae) and the subfamily Merliniinae, more than 500 soil s les were collected from various natural and agronomic habitats in the northern and north-western provinces of Iran. In this study, paratypes or populations of 22 species of Pratylenchoides , including the Iranian populations of P. alkani , P. crenicauda , P. erzurumensis , P. laticauda , P. nevadensis , P. ritteri and an undescribed species, were studied. Intra- and interspecies variation of the following characters were investigated: position of the pharyngeal gland nuclei, shape of female and male head, striation of female tail terminus, number of lateral lines at mid-body and in phasmid region for females, presence of intestinal fasciculi, and shape of sperm. Combining morphological and molecular data prompted us to propose two clusters of related Pratylenchoides species. One cluster includes P. crenicauda , P. variabilis and P. erzurumensis , whereas the second cluster consists of P. alkani , P. nevadensis and P. ritteri . Our data point to a sister positioning of P. magnicauda vis-à-vis all Pratylenchoides species included in this research. Analyses of SSU rDNA (for family and subfamily relationships) and partial LSU rDNA sequences (for intrageneric relationships) data revealed: i ) the distal and nested positioning of all Pratylenchoidinae within the Merliniidae ii ) the single transition from ectoparasitism to migratory endoparasitism within the family Merliniidae corresponds with the current subfamily partitioning and iii ) support for the monophyletic nature of the genus Pratylenchoides .
Publisher: Springer Science and Business Media LLC
Date: 14-08-2015
DOI: 10.1007/S00249-015-1068-Z
Abstract: Annexin V is of crucial importance for detection of the phosphatidylserine of apoptotic cell membranes. However, the manner in which different amounts of phosphatidylserine at the membrane surface at different stages of apoptosis contribute to binding of annexin V is unclear. We have used a quartz crystal microbalance combined with dissipative monitoring (QCM-D) and neutron reflectivity to characterize binding of human annexin V to supported bilayers of different phospholipid composition. We created model apoptotic bilayers of 1-palmitoyl-2-oleoyl-sn-glycerophosphocholine and 1-palmitoyl-2-oleoyl-sn-glycerophosphoserine (POPS) in the ratios 19:1, 9:1, 6.7:1, 4:1, 3:1, and 2:1 (w/w) in the presence of 2.5 mM CaCl2. QCM-D data revealed that annexin V bound less to supported fluid lipid bilayers with higher POPS content (>25 % POPS). Neutron reflectivity was used to further characterize the detailed composition of lipid bilayers with membrane-bound annexin V. Analysis confirmed less annexin V binding with higher POPS content, that bound annexin V formed a discrete layer above the lipid bilayer with little effect on the overall structure of the membrane, and that the thickness and volume fraction of the annexin V layer varied with POPS content. From these results we show that the POPS content of the outer surface of lipid bilayers affects the structure of membrane-bound annexin V.
Publisher: Magnolia Press
Date: 03-12-2018
DOI: 10.11646/ZOOTAXA.4526.4.3
Abstract: Trichotylenchus gorganiensis n. sp. is described and illustrated based on morphological and morphometric data. The new species is characterized by its 760–1073 µm long body, conoid-rounded lip region continuous with the body contour and bearing 5–7 fine striae, 22.0–24.5 µm long stylet, basal pharyngeal bulb offset or slightly overlapping intestine, post-anal sac extending 50–73 % of the tail region, and cylindrical or subclavate tail with a striated terminus. Differences of the new species from the closely related species T. astriatus, T. astriatoides, T. changlingensis and T. papyrus are discussed. Photomicrographs and several taxonomic notes on 13 other species of Telotylenchinae, collected from Iran, are provided.
Contribution to a revision of the genus Pratylenchoides Winslow, 1958 (Nematoda: Merliniidae), with redescription of P. erzurumensis Yüksel, 1977 from Iran
Publisher: Magnolia Press
Date: 23-12-2014
DOI: 10.11646/ZOOTAXA.3900.3.2
Abstract: Morphological and morphometric studies were conducted on the populations and paratypes of 14 species of the genus Pratylenchoides, including P. alkani, P. acuticauda, P. arenarius, P. arenicola, P. bacilisemenus, P. crenicauda, P. erzurumensis, P. heathi, P. laticauda, P. ritteri, P. rivalis, P. sheri, P. utahensis and P. variabilis. In addition, P. erzurumensis was redescribed based on a bisexual population from western Iran. The conoid head of males is an additional diagnostic character of this species distinguishing it from the closely related P. laticauda and P. camachoi. Based on detailed study of the main characters, synonymies of P. arenarius with P. bacilisemenus and P. variabilis with P. crenicauda are proposed. Synonymy of P. alkani with P. ritteri is supported also by morphological and biological evidence. Some taxonomic notes are made on some other species of the genus. Finally, a diagnostic compendium and key is provided for species identification.
Publisher: Oxford University Press (OUP)
Date: 2022
Abstract: Neisseria gonorrhoeae causes the sexually transmitted disease gonorrhoea. The treatment of gonorrhoea is becoming increasingly challenging, as N. gonorrhoeae has developed resistance to antimicrobial agents routinely used in the clinic. Resistance to penicillin is wide-spread partly due to the acquisition of β-lactamase genes. How N. gonorrhoeae survives an initial exposure to β-lactams before acquiring resistance genes remains to be understood. Here, using a panel of clinical isolates of N. gonorrhoeae we show that the β-lactamase enzyme is packaged into outer membrane vesicles (OMVs) by strains expressing blaTEM-1B or blaTEM-106, which protects otherwise susceptible clinical isolates from the β-lactam drug amoxycillin. We characterized the phenotypes of these clinical isolates of N. gonorrhoeae and the time courses over which the cross-protection of the strains is effective. Imaging and biochemical assays suggest that OMVs promote the transfer of proteins and lipids between bacteria. Thus, N. gonorrhoeae strains secret antibiotic degrading enzymes via OMVs enabling survival of otherwise susceptible bacteria.
Publisher: Springer US
Date: 2022
DOI: 10.1007/978-1-0716-2449-4_15
Abstract: The NLRP3 inflammasome senses the activity of pore-forming toxins secreted by Staphylococcus aureus. The bacterial toxins compromise plasma membrane integrity which activates the NLRP3 inflammasome to induce host pore-forming proteins and cellular suicide, termed pyroptosis. Host cell death rates are routinely determined at pre-defined time points and on whole cell populations. To capture the dynamic interactions between bacterial pore-forming toxins and host cell death factors, we have applied live-cell imaging techniques capable of analyzing single cell events in real time. Here, we describe methods using live-cell imaging to determine the host responses, such as plasma membrane integrity, mitochondrial health, and apoptotic caspases, towards pore-forming toxins.
Publisher: Elsevier BV
Date: 03-2022
Publisher: Springer Science and Business Media LLC
Date: 17-08-2020
Publisher: American Society for Microbiology
Date: 20-08-2020
DOI: 10.1128/AAC.00013-20
Abstract: Innate immunity is crucial for the host to defend against infections, and understanding the effect of polymyxins on innate immunity is important for optimizing their clinical use. In this study, we investigated the potential toxicity of polymyxins on human macrophage-like THP-1 and neutrophil-like HL-60 cells. Differentiated THP-1 human macrophages (THP-1-dMs) and HL-60 human neutrophils (HL-60-dNs) were employed. Flow cytometry was used to measure the concentration-dependent effects (100 to 2,500 μM for THP-1-dMs and 5 to 2,500 μM for HL-60-dNs) and time-dependent effects (1,000 μM for THP-1-dMs and 300 μM for HL-60-dNs) of polymyxin B over 24 h.
Publisher: Public Library of Science (PLoS)
Date: 30-03-2018
Publisher: Royal Society of Chemistry (RSC)
Date: 2018
DOI: 10.1039/C8TB02465K
Abstract: ANX–PS–Phy cubosomes could be applied as a safe and robust drug delivery vehicle for targeting damaged, apoptotic cells in ocular diseases.
No related grants have been discovered for Seong Hoong Chow.