Urinary Tract Infections Through the Lens of the Urinary Microbiome

Abstract

The misconception of a sterile urinary tract has been overturned in the past 20 years, leading to a burgeoning field of urinary microbiome research. While Escherichia coli is the predominant cause of urinary tract infections (UTIs), a diverse range of bacteria can also inhabit the urinary tract and cause UTIs. Non-E. coli members of the urinary microbiota remain understudied. Similarly, standardized methods for studying the urinary microbiome remain lacking. This dissertation integrates bioinformatics and bacterial pathogenesis approaches to investigate the urinary microbiome and specific commensal and pathogenic bacteria. Using clinical samples, I examine the composition and functional roles of urinary microbiota in health and disease. Chapter 2 establishes methodologies for studying the infant urinary microbiome and characterizes the Actinotignum genera, an opportunistic urinary pathogen. Chapter 3 links urinary microbiota composition to symptoms in patients with interstitial cystitis/bladder pain syndrome. In Chapter 4, I describe urinary and fecal microbiota in children with spina bifida, identifying mechanisms of bacterial evolutionary adaptation to the urinary tract. These evolutionary changes offer intriguing targets for therapeutic development against urinary pathogens. Chapter 5 explores the pathogenesis of Pseudomonas aeruginosa, revealing its intracellular behavior and respiratory strategies in bladder infection. Collectively, this dissertation integrates sequencing- and culture-based methods to characterize the urinary microbiome across diverse urologic diseases, revealing microbial colonization patterns, bacterial adaptation mechanisms, and host-pathogen interactions relevant to UTI pathogenesis. These findings establish a methodological and conceptual foundation for future mechanistic studies and therapeutic development targeting urinary tract diseases.