Molecular Mechanisms of Trichomonas Infection

• Antragsteller: Professor Dr. William Martin
• Fachliche Zuordnung: Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2013 bis 2016
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 231258561

Trichomonas vaginalis is the causative agent of Trichomoniasis, the most widespread non-viral sexually transmitted disease in humans. Infection involves O2-poor niches, host cell recognition, Fe2+-sequestration, morphogenesis of the parasite from flagellate to amoeboid form upon contact with host tissue, resistance to metronidazole treatment, as well as energy metabolism in and protein import into hydrogenosomes, the anaerobic mitochondria of trichomonads. Current knowledge about the molecular processes and mechanisms of Trichomonas infection is limited. In particular the very early stages of infection and host-parasite interactions are largely uncharacterized. Here we propose a concerted effort of two leading European laboratories working on trichomonad biology to uncover the molecular processes underlying infection by Trichomonas vaginalis of human urogenital tract tissue. The questions in the foreground of our proposal include i) the nature of parasite adherence, ii) changes in core carbon and energy metabolism during infection, and iii) the parasites transcriptomic response upon contact with host tissue. Our approach entails deep-sequencing of transcriptomes during early infection, combined with proteomics and biochemical characterization of individual components associated with hydrogenosomal import and function. To this end we have successfully established a stable in vitro infection system by combining the infectious T. vaginalis strain T016 and the human vaginal epithelial cell line MS74. The system has helped us not only to generate a rich source of novel preliminary data regarding the infection process, but furthermore allows new approaches to study hydrogenosomes, which harbor the target of metronidazole treatment.

• DFG-Verfahren: Sachbeihilfen
• Internationaler Bezug: Tschechische Republik
• Partnerorganisation: Czech Science Foundation
• Beteiligte Personen: Professor Dr. Sven B. Gould; Professor Jan Tachezy