Antiparasitic Agents; Drug Resistance
Drug resistance poses a serious problem in the treatment of many infectious agents, including anaerobic parasites (Trichomonas vaginalis, Giardia lamblia) and anaerobic bacteria (Helicobacter pylori, Clostridium spp., Bacteroides spp.). The main focus of our research lies on the molecular mechanisms causing resistance to metronidazole and other nitroheterocycle drugs which are prescribed against anaerobic infections. The redox system of anaerobic microorganisms seems to have a critical role as a target but also of an enhancer of nitroheterocycle toxicity. We study this dual role in several anaerobic microbes in order to discover a common theme and, eventually, remedies against nitroheterocycle resistance.
Techniques, methods & infrastructure
Molecular biological methods such as cloning, recombinant enzyme expression and biochemical enzyme assays. Two-dimensional gel electrophoresis (2DE), qPCR, western blotting.
- Nim-mediated metronidazole resistance in Bacteroides fragilis (2019)
Source of Funding: FWF (Austrian Science Fund), International research project
- Leitsch, D., Williams, C.F. & Hrdý, I., 2018. Redox Pathways as Drug Targets in Microaerophilic Parasites. Trends in Parasitology, 34(7), pp.576–589. Available at: http://dx.doi.org/10.1016/j.pt.2018.04.007.
- Leitsch, D., 2017. Drug susceptibility testing in microaerophilic parasites: Cysteine strongly affects the effectivities of metronidazole and auranofin, a novel and promising antimicrobial. International Journal for Parasitology: Drugs and Drug Resistance, 7(3), pp.321–327. Available at: http://dx.doi.org/10.1016/j.ijpddr.2017.09.001.
- Leitsch, D. et al., 2013. Trichomonas vaginalisflavin reductase 1 and its role in metronidazole resistance. Molecular Microbiology, 91(1), pp.198–208. Available at: http://dx.doi.org/10.1111/mmi.12455.
- Leitsch, D. et al., 2009. Trichomonas vaginalis: metronidazole and other nitroimidazole drugs are reduced by the flavin enzyme thioredoxin reductase and disrupt the cellular redox system. Implications for nitroimidazole toxicity and resistance. Molecular Microbiology, 72(2), pp.518–536. Available at: http://dx.doi.org/10.1111/j.1365-2958.2009.06675.x.
- Leitsch, D. et al., 2007. Nitroimidazole Action in Entamoeba histolytica: A Central Role for Thioredoxin Reductase G. E. Ward, ed. PLoS Biology, 5(8), p.e211. Available at: http://dx.doi.org/10.1371/journal.pbio.0050211.