# Host-cell mitochondrial alterations play a central role in EPEC pathogenesis

> **NIH NIH R01** · UNIVERSITY OF ARIZONA · 2020 · $370,211

## Abstract

ABSTRACT
The gastrointestinal pathogen enteropathogenic E. coli (EPEC) causes diarrhea and is responsible for
significant morbidity and mortality in children under five years of age in developing countries. There are
key gaps in our understanding of how EPEC causes diarrhea. The bacteria use a syringe-like type III
secretion system to deliver key virulence “effectors” directly into host intestinal epithelial cells. In the
initial phase of infection, EPEC delivers proteins that promote host cell survival. Later in infection,
however, secretion of more cytotoxic proteins results in host cell death. The studies proposed in this
application focus on two EPEC effector molecules that are secreted at discrete times post-infection,
and that have contrasting impacts on mitochondria, and on host cell survival. We hypothesize that the
orchestrated and intersecting actions of effector proteins on host mitochondrial stability and function
are critical for EPEC colonization and virulence. This hypothesis will be tested in three Aims where we
will: (1) Mechanistically define the impact of two EPEC effectors on host mitochondrial structure, (2)
Characterize effector-dependent alterations in mitochondrial function in infected intestinal epithelial
cells in vitro, and (3) Establish the impact of EPEC secreted virulence effectors on mitochondrial
function in vivo using a rabbit model of infection. The proposed studies will establish the precise role of
key secreted virulence factors, and of host mitochondrial perturbations, in EPEC virulence. In the future,
we anticipate our studies to inform the development and use of host cell-targeted molecules as adjuncts
to standard therapies for treating the diarrhea caused by EPEC and related bacteria.

## Key facts

- **NIH application ID:** 9944443
- **Project number:** 5R01AI141626-02
- **Recipient organization:** UNIVERSITY OF ARIZONA
- **Principal Investigator:** V K VISWANATHAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $370,211
- **Award type:** 5
- **Project period:** 2019-06-07 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9944443

## Citation

> US National Institutes of Health, RePORTER application 9944443, Host-cell mitochondrial alterations play a central role in EPEC pathogenesis (5R01AI141626-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9944443. Licensed CC0.

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