# Innate defenses against enterotoxigenic E. coli as potential therapeutic contributors

> **NIH NIH P01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $561,075

## Abstract

PROJECT SUMMARY
The bacterial pathogen enterotoxigenic E. coli (ETEC) contributes to the global burden of diarrheal disease
because vaccine protection and therapy remain inadequate. A long-term goal is to improve knowledge of
innate immune responses to ETEC infection, as they are likely important for initiating durable adaptive
immunity. The objective of this project is to understand the innate immune defenses employed by human
intestine to sense and eliminate ETEC, thus informing strategies for vaccine and/or drug design. We will (Aim
1) characterize the recognition and response mechanisms employed by tissue resident macrophages and
neutrophils against ETEC infection. In a complementary inquiry, we will (Aim 2) assess antimicrobial peptides
(AMPs) released by epithelial and immune cells in response to ETEC that could serve as potential treatment.
These aims will be explored in primary co-culture models of human small intestinal epithelium (tissue-derived
enteroids) and immune cell types from peripheral blood that are assembled on scaffolds to facilitate
physiologically relevant crosstalk between bacteria, epithelia, and immune cell populations. Model
development, application of anaerobic environment to mimic conditions in the intestinal lumen, and
characterization will combine the expertise of the Enteroid and Immunology Cores that support this P01. The
proposed studies are significant in that they will indicate the molecular signal transduction involved in reacting
to and resolving ETEC infection without clinically overt inflammation, an understudied aspect of acute
pathogenic diarrheal disease. Results from these studies will be compared to findings from enteroaggregative
E. coli and Shigella pathogenesis proposals in this P01 to identify common effectors for therapeutic targeting.
The projects of this P01 will cumulatively innovate human primary epithelial and immune cell co-culture
strategies for host-pathogen research.

## Key facts

- **NIH application ID:** 10868689
- **Project number:** 5P01AI125181-09
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Jennifer Foulke-Abel
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $561,075
- **Award type:** 5
- **Project period:** 2016-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868689

## Citation

> US National Institutes of Health, RePORTER application 10868689, Innate defenses against enterotoxigenic E. coli as potential therapeutic contributors (5P01AI125181-09). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10868689. Licensed CC0.

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