"Metabolic Crossroads: GABA Synthesis in Trichomonas Vaginalis Infectio" by Yesha Dhruv
 

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Research Advisor: Dr. Nigel Yarlett (Director, MS BMB Program)

Document Type

Thesis

Abstract

This study examines the gamma-aminobutyric acid (GABA) synthesis pathway in Trichomonas vaginalis infection of human HCT-8 cells, focusing on key enzymatic processes in glutamate conversion to GABA and metabolic adaptations. The hypothesis tested was that T. vaginalis modulates GABA metabolism to enhance host cell invasion and adaptation. Infection time-point studies, RNA sequencing, and aldehyde dehydrogenase (ALDH) assays were conducted. Comparisons between T. vaginalis strains Casu 2 and Casu 2/MOZ 2 revealed distinct infection dynamics. Casu 2 rapidly attached and replicated within an hour, peaking at 24 hours, while Casu 2/MOZ 2 exhibited delayed replication, peaking at 48 to 72 hours, suggesting immune evasion mechanisms. ALDH assays showed a slight increase in activity in Casu 2-infected cells but no statistically significant differences across control and infected groups. RNA sequencing (2-hour postinfection) revealed upregulation of GABA metabolism-related enzymes, including glutamate dehydrogenase, GABA permease, and succinate semialdehyde dehydrogenase, indicating enhanced GABA synthesis and transport. Increased expression of ornithine decarboxylase and NADH oxidase suggested metabolic shifts supporting parasite survival. These findings highlight the regulation of the GABA pathway in T. vaginalis infection, suggesting its role in cellular homeostasis and parasite survival. The observed metabolic reprogramming may optimize energy production and infection persistence. Excessive GABA production could disrupt host neurochemical balance, influencing immune modulation and inflammation. This study provides insights into T. vaginalis metabolic strategies and underscores the need for targeted therapeutic approaches.

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