Author ORCID Identifier

https://orcid.org/0000-0002-6919-2632

Defense Date

2018

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Integrative Life Sciences

First Advisor

Jennifer M. Fettweis

Abstract

The vaginal microbiome plays an important role in reproductive health and pregnancy. It has coevolved with humans and has direct effects on reproductive success, rendering selective pressure more pronounced at this site. Herein, we probe coevolution of the vaginal microbiome using a systems-level approach. In Chapter 2, we examine the evolutionary trajectory of two vaginal Veillonellaceae phylotypes evolved from an ancestral gastrointestinal lineage to inhabit the vaginal niche. We present evidence of their divergence and subniche specification and describe their differential associations with vaginal infection and pregnancy. In Chapter 3, we identify ten bacterial taxa, predicted to contribute to the underlying pathology of the sexually transmitted infection trichomoniasis. This ‘pathogroup’, which has undergone conditional differentiation to thrive in the presence of T. vaginalis, includes previously undescribed organisms and putative symbionts. Lastly in Chapter 4, we present the first characterization of BspA proteins, multi-modal virulence factors, in the vaginal microbiome and provide evidence of their extensive horizontal transfer across diverse microbial lineages. We use homology modeling to demonstrate conservation of structural and functional characteristics of these proteins between diverse bacterial taxa and identify structural variants, potentially indicative of subtypes. These findings further our understanding of the contributions of individual bacterial species, bacterial communities and virulence determinants in the health and disease. Furthermore, they lay the groundwork for future work characterizing coevolution of the human vaginal microbiome. These systems-level approaches will facilitate synergy between broad and reductive approaches and inform strategies for modulation of the microbiome and development of more effective therapeutics.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

5-9-2018

Available for download on Monday, May 08, 2023

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