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

> **NIH NIH P01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $1,581,962

## Abstract

Abstract
The development of human enteroids as a model to study the human intestine offers tremendous opportunities
to study the pathogenesis of infectious enteric disease. We propose to combine the substantial expertise from
three institutions with long and impressive histories in the investigation of enteric diseases to exploit this
powerful model to study the pathogenesis of four major etiologic agents of diarrheal disease: three pathotypes
of diarrheagenic E.coli (enteroaggregative, enterohemorrhagic and enterotoxigenic E. coli) and Shigella.
Investigators from the University of Maryland, Johns Hopkins University and the University of Virginia will
collaborate in this Program Project Grant (PPG). The leadership team of this PPG comprises three
internationally renowned experts in enteric diseases, with complementary training in microbiology,
gastroenterology, molecular physiology, and pediatric infectious diseases. They will direct a multidisciplinary
team of co-investigators with expertise in cell biology, molecular pathogenesis, and mucosal immunology. The
overall goal is to increase understanding of the pathophysiology and potential treatments of these four
important pathogens. The proposed studies will use normal human mini-intestines, called enteroids or
colonoids, grown on monolayers to develop models that mimic human disease. Examination of
pathophysiologic aspects common to the diseases studied will serve to integrate the projects. These aspects
include the role of mucins, bacterial proteases called SPATES, enterotoxins and secreted cytokines and are in
addition to pathophysiologic aspects specific to each infection. In addition, the contribution of cells involved in
innate immunity will be examined by co-culture of the enteroids/colonoids with human macrophages,
neutrophils and dendritic cells. These studies using human mini-intestines offer the possibility of revealing
insights in disease pathophysiology that are specific to normal human intestine rather than the animal models
and cancer cell line models used until now. Each of the four projects focuses on a specific pathogen:
enteroaggregative E. coli, Shigella, enterohemorrhagic E. coli, entertoxigenic E. coli. Besides an Administrative
Core, there is an Enteroid Core that provides human enteroids/colonoids and growth media, instructs all
projects on how to produce enteroid/colonoid monolayers and an Immunology Core that measures cytokines
and chemokines, and isolates human macrophages, neutrophils and dendritic cells. The Enteroid and
Immunology Cores work together to develop co-culture systems of innate immune cells and
enteroids/colonoids that will be used by the projects. The investigators will regularly interact by monthly joint
laboratory meetings. The proposed project will yield many significant new insights into enteric disease caused
by these important pathogens.

## Key facts

- **NIH application ID:** 9982173
- **Project number:** 5P01AI125181-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** MARK DONOWITZ
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,581,962
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982173

## Citation

> US National Institutes of Health, RePORTER application 9982173, Pathogenesis of E. coli and Shigella infections in human enteroid models (5P01AI125181-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9982173. Licensed CC0.

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