Evolution@Vanderbilt

Urinary tract infections (UTIs) are among the most frequent bacterial infections, are highly prevalent among women and have a high degree of recurrence. Currently, antibiotics are the primary treatment option for UTI, however they are increasingly failing to eliminate infection, they perturb the host microbiota and select for increased antibiotic resistance. This means that there is a pressing need for the development of alternative strategies for preventing and/or treating UTIs. Uropathogenic Escherichia coli (UPEC), which causes the majority of community- and hospital-acquired UTIs follows a transient intracellular lifestyle in the bladder that allows it to evade host immune defenses and establish reservoirs that perpetuate acute infection and recurrence. Part of this lifecycle includes the formation of biofilm-like communities inside bladder cells, in addition to forming extracellular biofilms on host cell surfaces and on catheter implants. My lab is studying: (1) The ways in which UPEC can sense changes in its surrounding environment and thereby accordingly alter its behavior as it transits through different host and environmental niches. We specifically studying the contribution of closely related interacting signaling networks in mediating bacterial behavior. (2) The factors contributing to and the hierarchy of biofilm formation, aiming to define specific stages in the pathway that can be targeted therapeutically. To achieve our goals, we use a wide variety of approaches, including classical genetics/molecular biology tools, cell-based and in vitro assays, chemical biology, the excellent -omics cores available to us through VU and VUMC, robust mouse and 3D-tissue models of UTI, as well as partnerships with urology colleagues that allow us to perform longitudinal studies investigating E. coli isolates from humans.