The Role of Lipophosphoglycan in the Pathogenesis of Trichomonas Vaginalis Infection

The Role of Lipophosphoglycan in the Pathogenesis of Trichomonas Vaginalis Infection

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Trichomonas vaginalis is the causative agent of the most common, non-viral sexually transmitted infection. T. vaginalis infection has been correlated with many complications, including premature labor, low-birth weight infants, cervical cancer and an increased susceptibility to HIV infection. Despite its prevalence and medical importance, the pathogenesis of T. vaginalis infections is poorly understood. Because T. vaginalis is an obligate extracellular pathogen, adherence to epithelial cells is critical for the establishment and maintenance of infection. The surface of T. vaginalis is covered with a dense glycocalyx composed mainly of lipophosphoglycan (LPG). The abundance and uniqueness of T. vaginalis LPG prompted us to study whether this molecule was involved in the attachment of parasites to host cells. In this study, we demonstrate that T. vaginalis LPG is an attachment factor for the parasite, and an altered LPG leads to reduced adherence and cytotoxicity of the parasite. We also demonstrate that human galectin-1 expressed by cervical epithelial cells binds to T. vaginalis LPG and crosslinks parasites to host cells, and thus identify the first host cell receptor for this parasite. While the structure of T. vaginalis LPG is unknown, the lipid and monosaccharide composition of the molecule is known, which allowed us to search the recently sequenced T. vaginalis genome for genes that are involved in the synthesis and assembly of the LPG molecule. Results from these searches have provided attractive new drug targets for this important parasite. Finally, the host innate immune system can detect unique structures such as LPG on microbial pathogens and respond accordingly. We therefore tested the effect of a cationic innate immune effector antimicrobial peptide that could potentially bind negatively charged LPG on T. vaginalis. Taken together, our data shed light on the molecular mechanisms of pathogenesis of T. vaginalis infection, and provide a foundation for future studies to combat this important parasitic disease.Miller, W.C. and J.M. Zenilman (2005) Epidemiology of chlamydial infection, gonorrhea, and trichomoniasis in the United ... and M.S. Cohen (2007) Trichomonas vaginalis infection in male sexual partners: implications for diagnosis, treatment, anbsp;...

Title:The Role of Lipophosphoglycan in the Pathogenesis of Trichomonas Vaginalis Infection
Author:Cheryl Yoshi Matheny Okumura
Publisher:ProQuest - 2008


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