Urinary tract infection (UTI) is the world\u27s most common bacterial infection. Much is known about the infectious process (pathogenesis) of a few of the bacteria that cause these infections, especially E. coli. Unfortunately, the pathogenesis of E. coli and other uropathogenic bacteria was explored almost exclusively in the belief that the bladder is supposed to be sterile. Our recent evidence, however, debunks this dogma. We used modern methods to reveal diverse bacterial communities in the bladders of adult women. These communities differ in women with and without lower urinary tract symptoms (LUTS), including UTI and urinary incontinence (UI). Many bacteria that we have detected in women with LUTS are understudied precisely because they were previously undetected or overlooked. Thus, very little is known about their pathogenesis. Aerococcus urinae is one of those understudied uropathogenic bacteria. It is associated with both UTI and UI. It is highly resistant to many antibiotics and, when undiagnosed, can cause invasive and life-threatening sepsis. Thus, I have begun a study of A. urinae\u27s pathogenesis. For well-studied uropathogens, the earliest stages of pathogenesis involve attachment to the cells that line the bladder wall (urothelium) and subsequent disruption of the host\u27s bladder immune system. I hypothesized that A. urinae also attaches to the urothelium and alters signaling to the host\u27s bladder immune system. To test my hypothesis, I first studied in vitro phenotypes of A. urinae related to attachment and colonization of the urothelium. Then, I studied the interaction between human urothelium and A. urinae strains isolated from womenwith LUTS. Results from this dissertation could be used to develop therapies that specifically target A. urinae
