Project description:We aimed to delineate mechanisms of T. vaginalis resistance using transcriptome profiling of metronidazole (MTZ)-resistant and sensitive T. vaginalis clinical isolates.
Project description:Trichomonas vaginalis is a sexually transmitted infection that causes vaginitis and increases the risk of HIV transmission. We are interested in the secreted and membrane glycoproteins of Trichomonas because they are likely involved in pathogenesis and may include novel vaccine targets. Four mass spectrometric methods (identification of all parasite proteins, glycoprotein enrichment with the plant lectin Concanavalin A, peptide:N-glycanase treatment to identify occupied N-glycans sites, and analysis of N-terminal peptides) were used to identify >300 Trichomonas secreted and membrane proteins. The first group of these proteins, which were present in multiple genome copies and had homologs in diverse eukaryotes, included 1) those involved in the N-glycan-dependent quality control protein folding in the ER lumen, 2) metalloproteases, serine proteases, cysteine proteases, and other lysosomal enzymes, and 3) transporters and membrane-associated cyclases. The second group of secreted and membrane proteins were, for the most part, encoded by single copy genes, unique to Trichomonas, and missing N-terminal signal peptides. The latter observation is despite evidence that the signal peptide peptidase functions normally in Trichomonas. As the unique secreted and membrane proteins of Trichomonas were often large and lacked features that make it easy to choose vaccine candidates, alternative strategies for vaccination and/or therapy are discussed.
