Molecular and biochemical characterisation of a thioredoxin-linked thiolperoxidase system in the hydrogenosomes of the microaerophilic parasite Trichomonas vaginalis

• Antragstellerin: Privatdozentin Dr. Katrin Henze
• Fachliche Zuordnung: Parasitologie und Biologie der Erreger tropischer Infektionskrankheiten
• Förderung: Förderung von 2007 bis 2009
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 35388627

With 180 million cases per year trichomoniasis is the most prevalent non-viral sexually transmitted infection world wide. The elevated risk of HIV infection connected to trichomoniasis and emergence of resistance to the most important drug in trichomoniasis treatment, metronidazole, has raised the need to study trichomonads, and especially their unique ATP-generating organelles, the hydrogenosomes, in detail. Hydrogenosomes, which harbour oxygen-sensitive enzymes like pyruvate:ferrodoxin oxidoreductase and Fe-hydrogenase, actively consume oxygen and produce H2O2 via oxygen-inducible Superoxide dismutase. Curiously, no enzymes capable of reducing H2O2 or alkyl peroxides have so far been identified in the organelles, raising the question how these highly deleterious compounds are detoxified in hydrogenosomes. In an ongoing proteome analysis of Trichomonas vaginalis hydrogenosomes we have identified two novel proteins with strong similarity to two putative prokaryotic peroxidases, rubrerythrin and the small periplasmic thiol peroxidase Tpx, which seem to be differentially regulated under oxidative stress. Both Tpx and rubrerythrin were previously found in many prokaryotes but not in other eukaryotes, suggesting a significant prokaryotic contribution to the oxygen-detoxification system of trichomonad hydrogenosomes. We propose to analyse the biochemical activity of Tpx and its putative electron-donating system thioredoxin/thioredoxin reductase in hydrogenosomes, as well as transcriptional and translational regulation of these proteins under oxidative stess, in oder to understand the mechanisms of oxidative stress protection in hydrogenosomes of trichomonads.

• DFG-Verfahren: Sachbeihilfen