Identification of key host proteins governing Trichomonas vaginalis : a host-parasite interaction study

Abstract

Trichomonas vaginalis is a flagellated extracellular protozoan parasite that causes Trichomoniasis, a chronic infection in the vaginal and prostate epithelium of humans. Current treatments combating T. vaginalis infections are effective but there is a trend of increasing resistance to 5- nitromidazoles which are the main class of drugs used to treat trichomoniasis. To date, the majority of research has focused on the parasite and little research has involved the host. Parasites cannot live without their host which suggests that the host must be contributing something other than just a refuge for the parasite. This project studies T. vaginalis host-parasite interactions, specifically with the aim to identify how host proteins may be involved in the establishment and maintenance of T. vaginalis infection. The goal of this project was to interact T. vaginalis with HeLa mammalian cervical epithelial cells, with the view to identify upregulated and downregulated proteins using sequential window acquisition of all theoretical fragment ion spectra (SWATH) proteomics. A proof of principle study was also undertaken by knocking out the host receptor galectin-1 using CRISPR/Cas9 technology. Our hypothesis is that allowing interaction of T. vaginalis with HeLa cells there will be potentially a number of upregulated and downregulated host proteins that may be manipulated by T. vaginalis, which play a key role in the infection process. 22 proteins were found to be differentially expressed, including proteins that may be manipulated by T. vaginalis. Proteins that were identified were found to have many different biological functions including the regulation of apoptosis, inflammation, cell cycle regulation and attachment. These proteins may be studied in future experiments to identify their biological significance to T. vaginalis infection. The galectin-1 knockout study produced a partial knockout of galectin-1 and could be used in future attachment studies once further optimization of the CRISPR knockout is performed.

Date of Award	2017
Original language	English