When our microbiota goes rogue: A possible inter-domain microbial interaction between Trichomonas vaginalis and bacteria of the human vaginal microbiota

Abstract

The human vaginal tract harbours a large number of microbes believed to play a role in influencing the outcome of vaginal infections. One specific vaginal microbiota composition, known as community state type IV (CST-IV), has been linked to an 8-fold increase in infections by the human protozoan parasite Trichomonas vaginalis, causative agent of the most common non-viral sexually transmitted disease, trichomoniasis. The combined effect of T. vaginalis and CST-IV bacteria on host cells is poorly understood. This thesis aims to address this knowledge gap by investigating interactions between T. vaginalis and the CST-IV bacteria, and particularly how this polymicrobial combination impacts the human vaginal epithelial cells (hVECs). Several complementary approaches were employed, including studies of microbial growth, antibiotic (metronidazole) resistance and interaction with the mucus layer; host cell studies of paracellular permeability, tight junction integrity, cytokine production, metabolic activity and early apoptosis. This research demonstrated for the first time that CST-IV bacteria aid T.vaginalis in not only resisting metronidazole treatment but also in propagating under unfavourable environmental conditions, reflecting nutrient-deprived vaginal conditions. Moreover, it was demonstrated in vitro that CST-IV associated bacteria assist the migration of T.vaginalis through the mucus layer. The combination of CST-IV bacteria and T.vaginalis adversely affects host cells by increasing paracellular permeability, due to decreased tight junction integrity, most likely due to a combined effect of cytokine and phosphatase production. It was also determined that CST-IV bacteria increase T. vaginalis adherence in a concentration-and contact-dependent manner, and induce early apoptosis of hVECs. In conclusion, this thesis shows that the anaerobic CST-IV bacteria increase pathogenicity of T. vaginalis and together these microorganisms synergistically affect the barrier function of the human vaginal epithelial cells. These findings establish the importance of microbiota composition in regards to trichomoniasis infection outcomes.