# Molecular Pathogenesis of Enterotoxigenic Escherichia coli Infections

> **NIH VA I01** · ST. LOUIS VA MEDICAL CENTER · 2022 · —

## Abstract

Enterotoxigenic Escherichia coli (ETEC) are an extraordinarily common cause of
infectious diarrhea in resource limited areas of the planet where military personnel are
frequently deployed. In endemic areas these pathogens are a major cause of morbidity
as well as mortality in young children. The acute illness associated with these
pathogens may range from mild diarrhea to severe, cholera-like disease associated with
rapid dehydration. Travelers and military personnel deployed to endemic regions are
highly susceptible to symptomatic illness caused by ETEC. Currently there is no vaccine
to prevent these infections. In addition to the acute illness these pathogens are
associated with a number of important but poorly understood sequelae including
malabsorption and tropical enteropathy, growth stunting, and cognitive impairment in
children as well as tropical malabsorption syndromes and irritable bowel syndrome in
returning travelers.
 ETEC are defined by the production of enterotoxins that lead to net export of salt
and water into the intestinal lumen. Most prior research effort has focused almost
exclusively on the cellular effects of these toxins that lead to diarrhea. However, recent
transcriptome studies of host cells following infection or treatment with toxin suggest
that these enterotoxins may impart many collateral effects relevant to our understanding
of key aspects of virulence associated with acute illness as well as the sequelae
associated with these infections. The proposed studies will focus on the interaction of
highly conserved E. coli fimbriae with a family of cell surface glycoproteins related to
carcinoembryonic antigen (CEA), the carcinoembryonic antigen cell adhesion molecules
(CEACAMs) that are expressed on intestinal epithelia. Interestingly our studies
demonstrate that these molecules are strongly up-regulated by ETEC heat-labile toxin
and that they may serve as a receptor for ETEC. Because these molecules play
essential roles in cellular adhesion and maintenance of tissue architecture, modulation
of their expression could play important roles in the sequelae associated with these
infections.

## Key facts

- **NIH application ID:** 10438532
- **Project number:** 5I01BX004825-03
- **Recipient organization:** ST. LOUIS VA MEDICAL CENTER
- **Principal Investigator:** James Michael Fleckenstein
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2022
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2020-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438532

## Citation

> US National Institutes of Health, RePORTER application 10438532, Molecular Pathogenesis of Enterotoxigenic Escherichia coli Infections (5I01BX004825-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10438532. Licensed CC0.

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