infection worldwide and is the most prevalent parasite found in the US population. Increased transmission of I THrWichoimnonwaosmenvagicnharliosnicaisllythe eintifoelcotgeidc wagitehnt thoisf tphaeramsitoest acnodmmtohne recneont-virianlcreasexuailnly thetranpspmeaitrtaendce of drug resistant strains warrant a better understanding of the biology of this understudied organism. The !proposed study aims to provide knowledge on the biogenesis and biochemistry of an unusual organelle, the hydrogenosome, that is present in T. vaginalis, but absent in its human host. This organelle is the target of the only drug licensed for therapy for trichomonasis, metronidazole. Our previous research on hydrogenosomes has led to a series of observations that indicate common properties are shared by hydrogenosomes and mitochondria, the equivalent organelle in host cells. However, distinct differences, Iwhich might be exploited for drug design, have also been discovered. In addition to its medical importance, knowledge of the protein composition of the hydrogenosome and phylogenetic analyses of lits components should help clarify how novel cellular structures and functions were acquired in early eukaryotes and assist in understanding how energy-generating organeUes evolved in the first eukaryotic cells 2-3 billion years ago. To this end, our overall goals are to understand properties of biogenesis and Ievolution of this organelle and establish its relationship to mitochondria.
Our specific aims are: (1) To elucidate the functions of hydrogenosomal membrane proteins and examine their possible roles in organelle biogenesis;(2) To identify hydrogenosomal presequence peptidases, using biochemical and bioinformatics approaches, and compare these with mitochondrial counterparts and (3) To begin to define the proteome of T. vaginalis hydrogenosomes. These studies will increase our understanding of the biogenesis, evolution and metabolic properties of organelles in eukaryotic cells, in addition to providing important new information on a novel organelle in this parasite.
|Wexler-Cohen, Yael; Stevens, Grant C; Barnoy, Eran et al. (2014) A dynamin-related protein contributes to Trichomonas vaginalis hydrogenosomal fission. FASEB J 28:1113-21|
|Leitsch, David; Janssen, Brian D; Kolarich, Daniel et al. (2014) Trichomonas vaginalis flavin reductase 1 and its role in metronidazole resistance. Mol Microbiol 91:198-208|
|Twu, Olivia; Johnson, Patricia J (2014) Parasite extracellular vesicles: mediators of intercellular communication. PLoS Pathog 10:e1004289|
|Schneider, Rachel E; Brown, Mark T; Shiflett, April M et al. (2011) The Trichomonas vaginalis hydrogenosome proteome is highly reduced relative to mitochondria, yet complex compared with mitosomes. Int J Parasitol 41:1421-34|
|Shiflett, April M; Johnson, Patricia J (2010) Mitochondrion-related organelles in eukaryotic protists. Annu Rev Microbiol 64:409-29|