My lab is focused on understanding the survival and virulence strategies employed by a group of important bacterial pathogens collectively known as Extraintestinal Pathogenic Escherichia coli, or ExPEC. These bacteria have a broad host range and display a remarkable ability to adapt to widely varying environmental conditions, often facing nutrient limitations, antibiotics, and aggressive host defense mechanisms. In humans, ExPEC can efficiently colonize the gastrointestinal tract like commensal strains, but have the added capacity to disseminate and cause disease in other host niches, including the bloodstream, central nervous system, and the urinary tract. Infections caused by ExPEC are among the most common and costly on the planet. Making matters worse is the recent global dissemination and expansion of multidrug-resistant ExPEC strains that cannot be treated with frontline antibiotics.
We are working to delineate both bacterial and host factors that control the ability of ExPEC to colonize and persist within diverse host environments, with a major goal being the development of improved anti-bacterial therapeutics. This research utilizes genetics, microscopy, biochemistry, global gene expression analysis, and molecular biology techniques coupled with cell culture, mouse, and zebrafish infection model systems. Specific goals of this research include:
1) Defining the mechanisms by which ExPEC invades, traffics, multiplies, and persists within host cells and tissues.
2) Identify and functionally define bacterial fitness and virulence factors, including small regulatory RNAs and other regulators, which enable ExPEC isolates to resist the multitude of environmental stresses encountered during the course of an infection.
3) Determining how ExPEC-associated toxins and other virulence factors modulate and hijack host signaling events, including host cell death, survival, and inflammatory pathways.