Improved Resolution of Prevotella Species, Strains and Genes Reveals TheirDiversity and Virulence Potential in the Female Genital Tract

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2021-01-29
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Abstract
Bacteria belonging to the genus Prevotella inhabit numerous human body sites, including the female genital tract. Although Prevotella species commonly, and often benignly colonize the vagina, their increased abundance is associated with the dysbiotic condition bacterial vaginosis (BV). Prevotella isolates are also routinely cultured from women experiencing upper genital tract infection and the genus has repeatedly been associated with preterm birth, but the ascending species and mechanisms involved are poorly understood. I developed a new bioinformatics tool that enabled me to ask, for the first time, whether genital Prevotella species encode the Type IX Secretion System, a feature that could contribute to their niche adaptation and virulence (Chapter II). The other objective of my thesis was to better define the phylogenetic breadth and genomic heterogeneity of Prevotella species that colonize the female genital tract. I sought to advance our understanding of how Prevotella impacts human pregnancy by: 1) Identifying the most prevalent and abundant Prevotella species in the lower vs. upper female genital tract; and 2) Performing the first comparative genomics study of the two most common vaginal Prevotella species, P. bivia and P. amnii, which have both been associated with preterm birth. I undertook these analyses using a multidisciplinary approach that included a systematic literature review (Chapter III), pangenome analysis (Chapter III), and a bioinformatics meta-analysis of 19 published microbiome datasets (Chapter IV). My research showed that genital Prevotella populations are much more diverse than previously appreciated, although relatively few genital Prevotella species were consistently detected in high abundance across cohorts. The correlated distribution of Prevotella species prevalence in the lower and upper genital tract suggests they may translocate via broadly conserved or passive mechanisms.The two most prevalent and closely related genital tract Prevotella species are genomically and functionally heterogeneous. Their distinct evolutionary history, driven by horizontal gene transfer and genome reduction, reflects both acquisition and loss of genes involved in evasion, adaptation, and niche partitioning. By expanding our understanding of genital Prevotella species diversity, and establishing parameters for their sensitive and specific detection, this work lays the foundation for future studies that will define the predictive and causal roles these enigmatic bacteria play in reproductive health.
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Bagheri, S. (2020). Improved Resolution of Prevotella Species, Strains and Genes Reveals TheirDiversity and Virulence Potential in the Female Genital Tract (Master's thesis, University of Calgary, Calgary, Canada). Retrieved from https://prism.ucalgary.ca.