Trichomonas pathogenesis: cell surface interactions

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DESCRIPTION (provided by applicant): Trichomonas vaginalis is the etiologic agent of the most common non-viral sexually transmitted infection (STI) worldwide and is the most prevalent parasite found in the US population. Increased transmission of HIV in women chronically infected with this parasite and a recent increase in the incidence of drug resistant Trichomoniasis warrant a better understanding of the biology of this understudied pathogen. 7. vaginalis infections are also associated with pre-term delivery, low birth weight and increased infant mortality in inner city America. Despite its global medical importance, the molecular mechanisms underlying the pathogenesis of T. vaginalis are virtually unknown. We have demonstrated a role for the glycocalyx that coats the surface of this parasite in host cell adherence and cytotoxicity and have identified the first putative host cell receptor for 7 vaginalis. We now propose to characterize molecules on the surface of 7. vaginalis and human vaginal epithelia cells (VECs) that may be critical for host-parasite interactions. To this end, we propose to (1) elucidate the structure of wild-type and mutant 7. vaginalis surface glycoconjugates and lipophosphoglycan (LPG) as a step towards identifying novel enzymes involved in its assembly, (2) delete the serine palmitoyl transferase 2 (SPT2) gene to create LPG null mutants and determine the effect on adherence and cytotoxicity of the parasite (3) validate candidate7 vaginalis genes required for the synthesis and assembly of the monosaccharide rhamnose, an unusual sugar that is absent in host cells and (4) examine the interaction between 7 vaginalis LPG and host cell galectin-1 (gal-1) and investigate whether this interaction plays a role in pathogenesis. In addition to providing critical data on the mechanisms underlying host-pathogen interaction of this prevalent STI, the proposed studies will yield information that may be useful for developing novel drug therapies and vaccination strategies.