Our lab is focused on identifying and studying the molecules and pathways that play critical roles during the interaction of bacterial pathogens with their hosts. We examine the host/pathogen interaction from both angles: the virulence mechanisms employed by bacteria to cause disease, and the mechanisms employed by the host to resist infection.
Enteropathogenic and Enterohemorrhagic Escherichia coli
The Gram-negative bacterium Escherichia coli is detected in the intestine of warm-blooded animals shortly after birth and persists for the lifetime of the host as part of the commensal microflora. Some E. coli strains, however, have evolved virulence mechanisms that enable them to cause a wide range of diseases in otherwise healthy individuals. Enteropathogenic E. coli (EPEC) is a diarrheal pathogen that kills several hundred thousand children each year in developing countries, while Enterohemorrhagic E. coli (EHEC) is more prevalent in developed countries and causes diarrheal outbreaks with potentially fatal complications. EHEC is typically food-borne and is transmitted to humans through the consumption of raw or undercooked meat, unpasteurized milk and juice, and manure-contaminated produce. Recent studies indicate that both the frequency of EHEC outbreaks and the severity of symptoms suffered are on the rise. These observations are all the more worrisome as there are no specific therapeutic regimens for EHEC infections: the use of antibiotics is not recommended because it is thought to exacerbate disease.
Virulence mechanisms of intestinal pathogens
EHEC and EPEC attach to intestinal epithelial cells and use a “molecular syringe,” the type III secretion system to inject bacterial virulence proteins directly into host cells. These proteins hijack host cell pathways to facilitate bacterial replication and survival, ultimately promoting disease. We identified nleA, a type III-translocated effector protein that is critical for virulence of EHEC and related pathogens. Current work in the lab is focused on investigating the molecular and physiological basis for nleA's striking effect on virulence, in order to understand its role in disease.
Genetic dissection of the host response to intestinal infection
While pathogenic bacteria have evolved sophisticated virulence mechanisms to cause disease within the host, the outcome of infection can vary greatly between individuals. To further understand the varying host response to these infections, we are applying a genetic approach to the Citrobacter rodentium mouse infection model to identify host genes and proteins that play critical roles in susceptibility/resistance to infection with EHEC and related pathogens.