ORCID Profile
0000-0002-6894-3000
Current Organisation
Robert Koch Institute
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Infectious Agents | Medicinal and Biomolecular Chemistry | Biologically Active Molecules
Expanding Knowledge in the Chemical Sciences | Expanding Knowledge in the Biological Sciences |
Publisher: Springer Science and Business Media LLC
Date: 20-10-2021
DOI: 10.1186/S40359-021-00645-Z
Abstract: The physical properties of tableware could influence selection and consumption of food and alcohol. There is considerable uncertainty, however, around the potential effects of different sizes and shapes of tableware on how much food and alcohol people self-serve. These studies aimed to estimate the impact of: 1. Plate size and shape on amount of food self-served 2.Wine glass and bottle size on amount of wine self-poured. 140 adults participated in two laboratory studies—each using randomised within-subjects factorial designs—where they self-served food (Study 1) and wine (Study 2): Study 1: 3 plate sizes (small medium large) × 2 plate shapes (circular square). Study 2: 3 wine glass sizes (small medium large) × 2 wine bottle sizes (75 cl 50 cl). Study 1: There was a main effect of plate size: less was self-served on small (76 g less, p 0.001) and medium (41 g less, p 0.001) plates, compared to large plates. There was no evidence for a main effect of plate shape ( p = 0.46) or a size and shape interaction ( p = 0.47). Study 2: There was a main effect of glass size: less was self-served in small (34 ml less, p 0.001) and medium (17 ml less, p 0.001) glasses, compared to large glasses. There was no evidence of a main effect of bottle size ( p = 0.20) or a glass and bottle size interaction ( p = 0.18). Smaller tableware (i.e. plates and wine glasses) decreases the amount of food and wine self-served in an initial serving. Future studies are required to generate estimates on selection and consumption in real world settings when numerous servings are possible. Protocol registration information : OSF ( osf.io/dj3c6/ ) and ISRCTN ( 10.1186/ISRCTN66774780 ).
Publisher: Elsevier BV
Date: 08-2016
DOI: 10.1016/J.MIB.2016.04.019
Abstract: Protozoan parasites have evolved erse growth and metabolic strategies for surviving and proliferating within different extracellular and intracellular niches in their mammalian hosts. Metabolomic approaches, including high coverage metabolite profiling and (13)C/(2)H-stable isotope labeling, are increasingly being used to identify parasite metabolic pathways that are important for survival and replication in vivo. These approaches are highlighting new links between parasite carbon metabolism and the ability of different parasite stages to colonize specific niches or host cell types. They have also revealed novel metabolic regulatory mechanisms that are important for homeostasis and survival in potentially nutrient variable environments. These studies highlight the importance of parasite and host metabolism as determinants of host-parasite interactions.
Publisher: Springer Science and Business Media LLC
Date: 04-03-2022
DOI: 10.1038/S41467-022-28730-W
Abstract: The apicomplexan parasite Toxoplasma gondii forms bradyzoite-containing tissue cysts that cause chronic and drug-tolerant infections. However, current in vitro models do not allow long-term culture of these cysts to maturity. Here, we developed a human myotube-based in vitro culture model of functionally mature tissue cysts that are orally infectious to mice and tolerate exposure to a range of antibiotics and temperature stresses. Metabolomic characterization of purified cysts reveals global changes that comprise increased levels of amino acids and decreased abundance of nucleobase- and tricarboxylic acid cycle-associated metabolites. In contrast to fast replicating tachyzoite forms of T. gondii these tissue cysts tolerate exposure to the aconitase inhibitor sodium fluoroacetate. Direct access to persistent stages of T. gondii under defined cell culture conditions will be essential for the dissection of functionally important host-parasite interactions and drug evasion mechanisms. It will also facilitate the identification of new strategies for therapeutic intervention.
Publisher: Elsevier BV
Date: 04-2023
Publisher: Public Library of Science (PLoS)
Date: 11-02-2019
Publisher: American Society for Microbiology
Date: 30-06-2020
Abstract: The Trypanosomatidae are protozoan parasites that infect insects, plants, and animals and have evolved complex monoxenous (single host) and dixenous (two hosts) lifestyles. A number of species of Trypanosomatidae, including Leishmania spp., have evolved the capacity to survive within intracellular niches in vertebrate hosts. The adaptations, metabolic and other, that are associated with development of intracellular lifestyles remain poorly defined. We show that genomes of Leishmania and Trypanosomatidae that can survive intracellularly encode a 2,4-dienoyl-CoA reductase that is involved in catabolism of a subclass of fatty acids. The trypanosomatid enzyme shows closest similarity to the corresponding bacterial enzymes and is located in the mitochondrion and essential for intracellular growth of Leishmania . The findings suggest that acquisition of this gene by lateral gene transfer from bacteria by ancestral monoxenous Trypanosomatidae likely contributed to the development of a dixenous lifestyle of these parasites.
Publisher: Elsevier BV
Date: 08-2015
DOI: 10.1016/J.CHOM.2015.07.008
Abstract: The expression of gluconeogenic enzymes is typically repressed when glucose is available. The protozoan parasite Toxoplasma gondii utilizes host glucose to sustain high rates of intracellular replication. However, despite their preferential utilization of glucose, intracellular parasites constitutively express two isoforms of the gluconeogenic enzyme fructose 1,6-bisphosphatase (TgFBP1 and TgFBP2). The rationale for constitutive expression of FBPases in T. gondii remains unclear. We find that conditional knockdown of TgFBP2 results in complete loss of intracellular growth in vitro under glucose-replete conditions and loss of acute virulence in mice. TgFBP2 deficiency was rescued by expression of catalytically active FBPase and was associated with altered glycolytic and mitochondrial TCA cycle fluxes, as well as dysregulation of glycolipid, amylopectin, and fatty acid biosynthesis. Futile cycling between gluconeogenic and glycolytic enzymes may constitute a regulatory mechanism that allows T. gondii to rapidly adapt to changes in nutrient availability in different host cells.
Publisher: Elsevier BV
Date: 07-2011
DOI: 10.1016/J.IJPARA.2011.03.005
Abstract: Apicomplexan parasites undergo metabolic shifts in adaptation to environmental changes. Here, we investigate the metabolic requirements which are responsible for ATP homeostasis in the extracellular stage of Toxoplasma gondii. Surprisingly, we found that freshly released tachyzoites are able to maintain a constant ATP level during the first hour of extracellular incubation without the acquisition of external carbon sources. We further demonstrated that the extent of gliding motility and that of host cell invasion is independent from the availability of external carbon sources during this one hour extracellular period. The ATP level and the invasion efficiency of extracellular parasites were severely decreased by treatment with the glycolysis inhibitor, 2-deoxy-d-glucose, but not by the F(0)F(1)-ATPase inhibitor, oligomycin. This suggests that although the uptake of glucose itself is not required during the 1h incubation period, extracellular parasites depend on the activity of the glycolytic pathway for ATP homeostasis. Furthermore, active glycolysis was evident by the secretion of lactate into the culture medium, even in the absence of external carbon sources. Together, our studies suggest that tachyzoites are independent from external carbon sources within the first hour of their extracellular life, which is the most relevant time span for finding a new host cell, but rely on the glycolytic metabolisation of internal carbon sources for ATP maintenance, gliding motility and host cell invasion.
Publisher: Cold Spring Harbor Laboratory
Date: 25-06-2021
DOI: 10.1101/2021.06.25.450001
Abstract: Intracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter Tg ApiAT1 functions in the selective uptake of arginine. Tg ApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify Tg ApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of Tg ApiAT6-1 in Xenopus laevis oocytes, we demonstrate that Tg ApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. Tg ApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T. gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by Tg ApiAT6-1 is ‘ trans -stimulated’ by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T. gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites. The causative agent of toxoplasmosis, Toxoplasma gondii , is a versatile intracellular parasite that can proliferate within nucleated cells of virtually all warm-blooded organisms. In order to survive, T. gondii must scavenge the cationic amino acids lysine and arginine from their hosts. In a previous study, we demonstrated that a plasma membrane-localized protein called Tg ApiAT1 facilitates the uptake of arginine into the parasite. We found that parasites lacking Tg ApiAT1 could proliferate when cultured in medium containing high concentrations of arginine, suggesting the existence of an additional uptake pathway for arginine. In the present study, we demonstrate that this second uptake pathway is mediated by Tg ApiAT6-1, a protein belonging to the same solute transporter family as Tg ApiAT1. We show that Tg ApiAT6-1 is the major lysine transporter of the parasite, and that it is critical for parasite proliferation. Furthermore, we demonstrate that Tg ApiAT6-1 can transport arginine into parasites in conditions where arginine concentrations are high and lysine concentrations are comparatively lower. These data support a model for the finely-tuned acquisition of essential cationic amino acids that involves multiple transporters, and which likely contributes to these parasites being able to survive and proliferate within a wide variety of host cell types.
Publisher: Proceedings of the National Academy of Sciences
Date: 04-08-2009
Abstract: Toxoplasma gondii , as an obligate intracellular and promiscuous pathogen of mammalian cells, utilizes host sugars for energy and to generate glycoconjugates that are important to its survival and virulence. Here, we report that T. gondii glucose transporter (TgGT1) is proficient in transporting mannose, galactose, and fructose besides glucose, and serves as a major hexose transporter at its plasma membrane. Toxoplasma harbors 3 additional putative sugar transporters (TgST1–3), of which TgST2 is expressed at its surface, whereas TgST1 and TgST3 are intracellular. Surprisingly, TgGT1 and TgST2 are nonessential to the parasite as their ablations inflict only a 30% or no defect in its intracellular growth, respectively. Indeed, Toxoplasma can also tolerate the deletion of both genes while incurring no further growth phenotype. Unlike Δ tgst2 , the modest impairment in Δ tggt1 and Δ tggt1 /Δ tgst2 mutants is because of a minor delay in their intracellular replication, which is a direct consequence of the abolished import of glucose. The Δ tggt1 displays an attenuated motility in defined minimal media that is rescued by glutamine. TgGT1-complemented parasites show an entirely restored growth, motility, and sugar import. The lack of exogenous glucose in Δ tggt1 culture fails to accentuate its intrinsic growth defect and prompts it to procure glutamine to sustain its metabolism. Unexpectedly, in vivo virulence of Δ tggt1 in mice remains unaffected. Taken together, our data demonstrate that glucose is nonessential for T. gondii tachyzoites, underscore glutamine is a complement substrate, and provide a basis for understanding the adaptation of T. gondii to erse host cells.
Publisher: F1000 Research Ltd
Date: 30-10-2018
DOI: 10.12688/F1000RESEARCH.16021.1
Abstract: Toxoplasma gondii is an obligate intracellular parasite belonging to the phylum Apicomplexa that infects all warm-blooded animals, including humans. T. gondii can replicate in every nucleated host cell by orchestrating metabolic interactions to derive crucial nutrients. In this review, we summarize the current status of known metabolic interactions of T. gondii with its host cell and discuss open questions and promising experimental approaches that will allow further dissection of the host–parasite interface and discovery of ways to efficiently target both tachyzoite and bradyzoite forms of T. gondii , which are associated with acute and chronic infection, respectively.
Publisher: Wiley
Date: 17-12-2010
DOI: 10.1096/FJ.10-173278
Publisher: Public Library of Science (PLoS)
Date: 25-08-2021
DOI: 10.1371/JOURNAL.PPAT.1009835
Abstract: Intracellular parasites of the phylum Apicomplexa are dependent on the scavenging of essential amino acids from their hosts. We previously identified a large family of apicomplexan-specific plasma membrane-localized amino acid transporters, the ApiATs, and showed that the Toxoplasma gondii transporter Tg ApiAT1 functions in the selective uptake of arginine. Tg ApiAT1 is essential for parasite virulence, but dispensable for parasite growth in medium containing high concentrations of arginine, indicating the presence of at least one other arginine transporter. Here we identify Tg ApiAT6-1 as the second arginine transporter. Using a combination of parasite assays and heterologous characterisation of Tg ApiAT6-1 in Xenopus laevis oocytes, we demonstrate that Tg ApiAT6-1 is a general cationic amino acid transporter that mediates both the high-affinity uptake of lysine and the low-affinity uptake of arginine. Tg ApiAT6-1 is the primary lysine transporter in the disease-causing tachyzoite stage of T . gondii and is essential for parasite proliferation. We demonstrate that the uptake of cationic amino acids by Tg ApiAT6-1 is ‘ trans -stimulated’ by cationic and neutral amino acids and is likely promoted by an inwardly negative membrane potential. These findings demonstrate that T . gondii has evolved overlapping transport mechanisms for the uptake of essential cationic amino acids, and we draw together our findings into a comprehensive model that highlights the finely-tuned, regulated processes that mediate cationic amino acid scavenging by these intracellular parasites.
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.CHOM.2015.11.004
Abstract: Transmissible stages of Toxoplasma gondii store energy in the form of the carbohydrate amylopectin. Here, we show that the Ca(2+)-dependent protein kinase CDPK2 is a critical regulator of amylopectin metabolism. Increased synthesis and loss of degradation of amylopectin in CDPK2 deficient parasites results in the hyperaccumulation of this sugar polymer. A carbohydrate-binding module 20 (CBM20) targets CDPK2 to amylopectin stores, while the EF-hands regulate CDPK2 kinase activity in response to Ca(2+) to modulate amylopectin levels. We identify enzymes involved in amylopectin turnover whose phosphorylation is dependent on CDPK2 activity. Strikingly, accumulation of massive amylopectin granules in CDPK2-deficient bradyzoite stages leads to gross morphological defects and complete ablation of cyst formation in a mouse model. Together these data show that Ca(2+) signaling regulates carbohydrate metabolism in Toxoplasma and that the post-translational control of this pathway is required for normal cyst development.
Start Date: 2012
End Date: 2014
Funder: German Research Foundation
View Funded ActivityStart Date: 2008
End Date: 2010
Funder: Helmholtz Association
View Funded ActivityStart Date: 2007
End Date: 2007
Funder: European Molecular Biology Organization
View Funded ActivityStart Date: 2017
End Date: 2011
Funder: German Research Foundation
View Funded ActivityStart Date: 2011
End Date: 2011
Funder: Helmholtz Association
View Funded ActivityStart Date: 2013
End Date: 2014
Funder: Deutsche Forschungsgemeinschaft
View Funded ActivityStart Date: 05-2022
End Date: 05-2025
Amount: $415,495.00
Funder: Australian Research Council
View Funded Activity