ORCID

https://orcid.org/0000-0001-5211-7524

Date of Award

9-11-2023

Author's School

Graduate School of Arts and Sciences

Author's Department

Biology & Biomedical Sciences (Molecular Microbiology & Microbial Pathogenesis)

Degree Name

Doctor of Philosophy (PhD)

Degree Type

Dissertation

Abstract

Bacterial vaginosis (BV) is a condition of vaginal flora that affects about 1/3 of reproductive age women. The optimal vaginal microbiome is thought to be one dominated by Lactobacillus species. In the BV-positive microbiome, this lactobacillus-dominance is replaced by an outgrowth of diverse anaerobic bacteria. BV has been clinically linked to a number of negative health outcomes, including preterm birth, infertility, cervical dysplasia, and an increased risk of sexually-transmitted infections (STIs) such as gonorrhea. The underlying cause(s) of BV have been debated in the literature for over half a century. In 1955, it was first reported that a bacterium now known as Gardnerella vaginalis may be the sole causative agent. However this theory has been met with controversy in the intervening decades, especially as it has become increasingly clear that BV is a polymicrobial condition involving many different species of bacteria. Nonetheless, G. vaginalis remains the most commonly isolated organism from the genital tract of women with BV, and 16S sequencing has revealed that it is often among the most abundant in the BV microbiome. There is also in vivo evidence that G. vaginalis infection alone is sufficient to trigger some clinical features of BV, or relevant health complications associated with the condition. In this thesis we use in vivo and in vitro models to investigate how Gardnerella may contribute to BV pathology. We specifically examined the hypothesis that Gardnerella is able to encourage colonization or virulence of other pathogens, by investigating its relationship with Neisseria gonorrhoeae. In the studies presented here we demonstrate that that cytolytic proteins produced by G. vaginalis can potentiate gonococcal immune evasion via glycan molecular mimicry. Additionally, we provide evidence for a mutualistic growth/survival phenotype between N. gonorrhoeae and Gardnerella when the two organisms are co-cultured in vitro. Taken together, these data suggest a role of Gardnerella in facilitating cervicovaginal colonization by N. gonorrhoeae, and provide insights into potential mechanism(s) underlying the clinical link between gonorrhea and BV.

Language

English (en)

Chair and Committee

Amanda Lewis

Committee Members

Michael Caparon

Included in

Microbiology Commons

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