College of Veterinary Medicine

Veterinary Microbiology and Pathology

Leigh Knodler

Leigh Knodler, PhD
Assistant Professor Paul G. Allen School for Global Animal Health
(509) 335-4046 (office)

Research Interests

The Gram-negative bacterium, Salmonella enterica, is a leading bacterial cause of food-borne illness in the USA and worldwide. Ingestion of Salmonella enterica leads to acute gastroenteritis in humans and some animal species, but exactly how this occurs is a key biological question that remains largely unanswered. My research applies cell biology, molecular biology, biochemistry and microscopy techniques to study the interaction of Salmonella enterica with in vitro models of intestinal epithelium. Using polarized intestinal epithelial cells, I discovered a novel means of bacterial egress, a phenomenon that might explain how Salmonella spreads within a host and to new hosts (Knodler et al., 2010). While Salmonella enterica has long been know to reside within a membrane-bound compartment, the Salmonella-containing vacuole, I identified a population of bacteria that escape from their vacuole and hyper-replicate in the nutrient-rich cytosol of intestinal epithelial cells. These cytosolic bacteria express a subset of virulence genes that are normally required for bacterial-mediated entry into host epithelial cells. The host cell senses the cytosolic bacterial burden and undergoes a pro-inflammatory form of cell death, pyroptosis, characterized by release of the pro-inflammatory cytokine, interleukin-18 (IL-18), and extrusion from the monolayer. Therefore, in a hallmark example of the tug-of-war at play between host and pathogen, the host expels “invasion-primed” bacteria into the luminal space, enabling bacteria to invade new epithelial cells.  

The overall aim of my research is to elucidate bacterial and host factors that dictate the intracellular fate of Salmonella enterica in intestinal epithelial cells, with the ultimate goal of gaining a better understanding of how enteropathogenic bacteria cause diarrheal disease.


Last Edited: Oct 30, 2012 4:05 PM   

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