# Modeling the Pathogenic Processes of Shigella in the Human Colonoid

> **NIH NIH P01** · UNIVERSITY OF MARYLAND BALTIMORE · 2020 · $262,650

## Abstract

Project 2: Modeling the Pathogenic Processes of Shigella in the Human Colonoid Model
Shigella is one of the most important diarrheal pathogens among children in developing countries. Recent
data from the Global Enteric Multicenter Study (GEMS) identified Shigella as the most important pathogen in
children in the two older age groups (encompassing children 12-59 months of age). Infections by this
pathogen result in severe outcomes, increasing antibiotic resistance is limiting therapeutic options and there is
no licensed vaccine for Shigella. The study of this enteric pathogen and advancement of new or improved
vaccines and therapeutics has suffered from a lack of preclinical models that reflect relevant human disease
pathophysiology. The human enteroid/colonoid “mini-gut” model presents a technological leap in human GI
system modeling that will allow identification of highly relevant host-pathogen interactions that are expected to
lead to the discovery of novel points of intervention for therapeutic options and vaccine development. We
propose to use this innovative system to answer questions about pathogenic processes that have not yet been
sufficiently explored, including mechanisms of entry and invasion, apical and basolateral surface contributions,
interactions with host cell factors including mucus, and the role of bacterial virulence factors including Pic. The
development of the multi-cellular colonoids grown as a monolayers on Transwell filters yields direct access to
both apical and basolateral surfaces which express physiologic mucus, facilitates the engraftment of immune
cells such as macrophages and dendritic cells and allows quantification of neutrophil transmigration. This
project will define optimal parameters for Shigella-colonoid infection studies that will allow identification of
critical pathogenic mechanisms, and host cell responses. Furthermore, this system will be developed to serve
as a preclinical model for evaluation of live attenuated Shigella vaccine candidates to accelerate advancement
of urgently needed intervention strategies.

## Key facts

- **NIH application ID:** 9982182
- **Project number:** 5P01AI125181-05
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Eileen M. Barry
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $262,650
- **Award type:** 5
- **Project period:** — → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9982182

## Citation

> US National Institutes of Health, RePORTER application 9982182, Modeling the Pathogenic Processes of Shigella in the Human Colonoid (5P01AI125181-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9982182. Licensed CC0.

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