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