We wish to define how strains or uropathogenic Escherichia coli (UPEC) and related bacterial pathogens colonize host tissues and persist in the face of numerous innate and adaptive defenses.

My lab is interested in understanding the mechanisms and consequences of bacterial interactions with host cells and tissues. Contact between a bacterial pathogen and its host is often mediated by microbial adhesive molecules known as adhesins and specific host cell receptors. Bacterial attachment to host receptors can initiate a cascade of molecular crosstalk between bacterial and host cells that can directly influence the outcome of an infection. Examination of the pathogenesis of urinary tract infections (UTIs) provides an excellent system to delineate host-pathogen interactions at the molecular, cellular, and tissue levels. UTIs affect a large proportion of the world population and account for significant morbidity and high medical costs. Strains of uropathogenic Escherichia coli (UPEC) are the primary causative agents of UTIs. In addition to UTIs, UPEC-related isolates, collectively known as extra-intestinal pathogenic E. coli (ExPEC), are responsible for a variety of other infections, including pneumonia, bacteremia, neonatal meningitis, deep surgical wound infections, and vertebral osteomyelitis. Within the urinary tract, UPEC isolates are able to bind and invade host epithelial cells. Once internalized, UPEC can either multiply or enter a quiescent, non-replicating state. Host stress and inflammatory response pathways along with host cytoskeletal components and virulence factors encoded by the pathogen all likely modulate intracellular growth and the eventual efflux of UPEC. Infection by UPEC stimulates a slew of anti-microbial, pro-inflammatory, pro-differentiation and host cell suicide pathways within the urinary tract. These host responses, in turn, can result in activation of stress response pathways and virulence gene expression in UPEC. Using genetics, microscopy, biochemistry, global gene expression analysis and molecular biology techniques coupled with cell culture, engineered tissue and mouse model systems, we are working to identify and characterize host and bacterial factors that allow UPEC and other pathogens to colonize and persist within host tissues. Specific research aims in the lab include:

1. Defining the mechanisms by which UPEC invades, traffics, multiplies, and persists within host epithelial cells.
2. Defining how ExPEC responds to and resists nitrosative and oxidative stress encountered during the course of an infection.
3. Determining how ExPEC modulates host cell death and survival pathways.