Date of Award

7-2-2024

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Department

Microbiology and Immunology

First Advisor

Alan Wolfe

Abstract

Aerococcus urinae is an uncommon inhabitant of the human urogenital tract. The Gram-positive bacterium has been implicated in a wide range of urinary tract diseases that, if left untreated or undiagnosed, can progress to severe disease such as infective endocarditis. Comparative analysis of 115 A. urinae isolates from infection episodes of urinary tract infection, bacteremia, infective endocarditis, urgency urinary incontinence, stress urinary incontinence, interstitial cystitis / painful bladder syndrome, and asymptomatic individuals reveal substantial diversity with respect to predicted virulence factors, metabolism, and observed biofilm behavior. Through whole genome sequencing analysis, these strains can be reorganized into six new taxonomic groups, representing a complex of species. The newly named species, A. tenax, A. mictus, and A. loyolae, and the newly defined A. urinae each display their own unique phenotypes including metabolism and flocking biofilm ability that allow each to be differentiated from one another. It is hypothesized that these species-specific behaviors confer pathogenic potential through tissue adherence, host-tissue tropisms, and growth dynamics. This study analyzes these differences through comparative genomics, identifying distinguishing features that can explain speciation. Among these features, horizontal gene transfer was found to play a significant role in genomic variation. Vectors such as integrative and conjugative elements (ICEs) were identified as key in introducing large genomic content such as antibiotic resistance genes. To facilitate rapid and unambiguous identification of these new species, a multiplex PCR test was created. This test was evaluated on 189 clinical isolates previously identified as A. urinae and successfully identified 88% of isolates. From this dataset, the species distribution in a tertiary hospital system was determined, finding that certain species are far more commonly isolated than others. It is anticipated that the findings of this study will lead to the development of better identification, detection, and diagnostic practices that will ultimately contribute towards treatment strategies preventing any Aerococcus infection from exacerbating to fatality. The strategies developed in this study can also be used as a template to investigate other poorly understood bacteria, particularly uncharacterized emerging uropathogens, broadening our understanding of the human urinary microbiome.

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