# Pathogenesis of E. coli and Shigella infections in human enteroid models

> **NIH NIH P01** · UNIVERSITY OF MARYLAND BALTIMORE · 2024 · $2,130,811

## Abstract

Pathogenesis of E. coli and Shigella Infections in Human Enteroid Models
 Overall Description / Summary
 This first renewal of a funded program Project Grant (PPG) is to continue progress in understanding the
pathophysiology and identification of ways to interfere with diarrhea caused by Shigella and two pathotypes of
diarrheagenic E. coli (enteroaggregative and enterotoxigenic E. coli). The substantial progress made has
resulted from the close collaboration and combined expertise of investigators from the University of Maryland,
Johns Hopkins University and the University of Virginia who are using shared models of normal human enteroid
and colonoid monolayers exposed to enteric bacterial pathogens as well as human enteroid monolayers co-
cultured with innate phagocytic cells present in the intestine. The group of investigators has internationally
renowned experience in enteric diseases, as well as in microbiology, gastroenterology, molecular physiology,
pediatric infectious diseases, cell biology, molecular pathogenesis, and mucosal immunology. This consortium
has interacted and in a superbly collaborative manner sharing technical and scientific information through formal
monthly face-to-face or Zoom-based meetings, frequent telephone or electronic communication and visits to
laboratories, with the latter being the standard form of interaction of the U Maryland and JHU investigators. The
Enteroid and Immunology Cores have developed new tools and methods that were rapidly transferred to the
Project investigators, resulting in a significant number of collaborative publications from the PPG. As expected,
progress was stepwise with transfer of methodology and reagents for propagating the enteroids, production of
monolayers, development of the bacterial-enteroid models, and development of co-cultures with immune cells
leading to new insights in the pathogen-enteroid interactions. The overall goal of the PPG remains to increase
understanding of the pathophysiology and potential treatments of these three important pathogens. The
proposed studies will continue to use normal human enteroids or colonoids, grown on monolayers, and extend
this through co-culture to make the model more closely resemble human intestine. This will be accomplished by
expanding the co-culture models to a) establish monolayers in a 3D scaffold matrix to facilitate epithelial-immune
cell interaction and immune cell movement; b) incorporate macrophages, neutrophils and dendritic cells as well
as to develop a new co-culture system that includes intraepithelial γδ +T lymphocytes (IEL); c) apply an enriched
M cell model; d) expose the co-culture model to flow-based shear stress as occurs normally in the intestine; e)
determine the contribution of an anaerobic environment. As during the past funding period, examination of
pathophysiologic aspects common to the diseases studied will serve to integrate the projects. In addition to
pathogen specific pathophysiologic aspects, these include...

## Key facts

- **NIH application ID:** 10868670
- **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:** $2,130,811
- **Award type:** 5
- **Project period:** 2016-07-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10868670

## Citation

> US National Institutes of Health, RePORTER application 10868670, Pathogenesis of E. coli and Shigella infections in human enteroid models (5P01AI125181-09). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10868670. Licensed CC0.

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