Elucidating Enterococcal Mechanisms Underlying Recurrent Urinary Tract Infections

Urinary tract infection (UTI) is one of the most common bacterial infections globally and can lead to life-threatening complications. UTI disproportionately affects females, with the majority of females being treated for at least one UTI in their lifetime. Of the females who develop UTI in their lifetime, almost one third will develop recurrence within six months after initial treatment and many will struggle with UTI recurrence for long spans of their lives. Although recurrent UTI has previously been attributed to persistence of Escherichia coli, recent studies utilizing more sensitive detection methods have shown Enterococcus faecalis is strongly associated with recurrent and chronic lower urinary tract symptoms. Because E. faecalis is largely regarded as a commensal organism pushed to an opportunistic pathogenic lifestyle in specific cases and the fact that roughly half of all E. faecalis-UTI cases are missed by standard detection methods, mechanisms underlying colonization and pathogenesis is understudied in the bladder. Currently, the understanding of enterococcal UTI is based on a small fraction of urinary E. faecalis isolates. This knowledge gap prevents the urobiome field from accurately identifying and studying enterococcal factors important for bladder colonization and establishment of persistent infection. Thus, this dissertation highlights the importance of E. faecalis in various lower urinary tract conditions and compares genetic profiles of urogenital E. faecalis isolates to determine factors that are enriched in cases of asymptomatic colonization, sporadic UTI, and recurrent UTI. Upon identification of bacterial factors unique to recurrent UTI isolates, additional experiments utilizing bladder organoids investigate their impact on the host response and overall environment.