Enterotoxigenic Escherichia coli

molecular microbiology, pathogenesis, and prevention

the pathogen

Our lab studies focus on Enterotoxigenic Escherichia coli (ETEC), a genetically diverse type of pathogenic E. coli defined by the productions of heat-labile (LT) and/or heat-stable (ST) toxins.

ETEC are responsible from hundreds of millions of cases of infectious diarrhea each year, predominately in low and middle income countries where young children are disproportionately affected.

In addition to acute diarrheal illness, which can range from mild to severe and cholera-like, ETEC have repeatedly been associated with important but poorly understood sequelae including malnutrition and stunting in children.

the mission

At present there is no licensed vaccine to prevent ETEC infections.

Nevertheless, the incidence of acute symptomatic illness in endemic regions declines with age suggesting that development of a vaccine is possible.

The overall mission of the laboratory is to investigate the molecular pathogenesis of ETEC.

By carefully dissecting the nature of pathogen-host interactions leading to acute illness as well as the contributions of ETEC infections and its toxins to sequelae we hope to inform the development of a broadly protective and inexpensive vaccine.

structure and function of ETEC toxins

Structure of ETEC toxins
Heat-labile toxin (LT, left) and heat-stable toxin (ST, right). LT is structurally similar to cholera toxin, while ST molecules are short peptides (18-19 amino acids) that mimic the structure and function of native intestinal peptides guanylin and uroguanlyin.
Canonical actions of ETEC toxins
ST stimulates the production of cGMP leading to activation of protein kinase G (PKG). LT stimulates production of cAMP leading to activation of protein kinase A (PKA). Both kinases phosphorylate cellular ion channels promoting the net accumulation of NaCl and water in the intestinal lumen.