# Interaction of enteropathogenic Yersinia and Vibrio cholera with engineered human intestinal tissue

> **NIH NIH U19** · TUFTS UNIVERSITY BOSTON · 2021 · $532,840

## Abstract

ABSTRACT
Enteric infections caused by bacterial pathogens are often debilitating and life-threatening, especially for young
children. In vivo rodent models and in vitro intestinal epithelial cell monolayers, the most common models for
studying these pathogens, often do not recapitulate the true outcomes of enteric infections that occur in the
human intestine. Therefore, many aspects of the interactions between these pathogens and the human host
remain unknown. This project aims to dissect the early events between cells in the human small-intestine and
two important intestinal enteric pathogens, Vibrio cholerae and Yersinia pseudotuberculosis, using a
multicellular 3D in vitro human tissue model that incorporates flow, low 02 tension, immune cells and normal
microbiota. Specifically, we will use silk proteins as scaffolds to develop a 3D multicellular matrix system to
support human intestinal epithelium formation for sustained cultivation and for infection by enteric pathogens.
These silk scaffolds will be seeded with cells from enteroids derived from children. Our preliminary data shows
that these 3D silk scaffolds that are seeded with cells from ileal enteroids develop at least 4 major intestinal cell
types when placed in differential medium. Building on these results, this project will continue to develop and
study these intestinal tissues by sequentially introducing flow dynamics, physiological concentrations of 02
(5%), immune cells, and normal microbiota into these 3D ileal tissues scaffolds. Our goals are to understand (1)
how, where and the consequences of V. cholerae and Y. pseudotuberculosis binding to and damaging the
human intestine under conditions of flow and low 02; (2) the bacterial and host transcriptomes after infection of
this human tissue model; (3) the impact of neutrophils on colonization, damage and host responses to infection;
(4) the impact of specific Y. pseudotuberculosis adhesins and Yops on this human intestinal model; and (5) the
impact of V. cholerae quorum sensing on its colonization; and (6) the impact of interspecies communication
between V. cholerae or Y. pseudotuberculosis and normal microbiota on colonization and tissue damage. In
addition, we will probe the utility of this model for assessing anti-infectives by testing a number of small
molecules that disrupt quorum sensing or type 3 secretion systems on the colonization and damage caused by
these pathogens. Establishing this tunable 3-D intestinal system will permit the development of methods that
interrupt seeding, spread and/or damage by the pathogen by targeting specific bacterial mechanisms or by
supplementing the host with specific microbiota or other factors that compete for the same niches, inhibit
colonization, and/or reduce intestinal damage and inflammation.

## Key facts

- **NIH application ID:** 10135007
- **Project number:** 5U19AI131126-05
- **Recipient organization:** TUFTS UNIVERSITY BOSTON
- **Principal Investigator:** Joan C Mecsas
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $532,840
- **Award type:** 5
- **Project period:** 2017-04-07 → 2023-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10135007

## Citation

> US National Institutes of Health, RePORTER application 10135007, Interaction of enteropathogenic Yersinia and Vibrio cholera with engineered human intestinal tissue (5U19AI131126-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10135007. Licensed CC0.

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