# Bioelectricity in Gut Epithelium Drives Pathogenic Bacterial Targeting

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2022 · $196,250

## Abstract

Project Summary
Our gut contains about 100 trillion commensal bacteria that collectively contribute to nutrient absorption and
maturation of the immune system, as well as play a central role in protecting the host from enteric bacterial
infections. However, many enteric bacterial pathogens have developed strategies to colonize the intestinal
mucosa and cause diseases. Clinically significant enteric bacteria, such as Salmonella, Shigella, Yersinia, and
pathogenic E. coli, are a major public health concern due to their pathogenic capacities to cause severe
diarrheal and extraintestinal diseases with potentially fatal consequences, and their ease of transmission
through contaminated food and water. These bacteria have developed common strategies to specifically target
and invade a relatively small number of follicle-associated epithelial (FAE) cells known as Microfold (M) cells to
induce inflammation. Contamination with extremely low doses, sometimes with only a few pathogens, can
cause severe enteritis and/or disseminated infections. It remains poorly understood how so few bacterial
pathogens, which are typically surrounded by millions (if not billions) of commensal microbes, find a way to
their targeted portal of entry—the low abundance M cells of the FAE.
 Previously, we have demonstrated the existence of endogenous bioelectric fields in the tracheal mucus
epithelium of the rhesus monkey and, and for the first time, detected Salmonella infection-generated electric
fields (IGEF) in mouse cecum FAE. These bioelectrical signals play critical roles during embryonic
development, tissue regeneration and wound healing, as well as in disseminated infections as we demonstrate
in our most recent work. By applying electric fields mimicking IGEF we have shown that commensal E. coli
migrate to the anode and pathogenic Salmonella migrate to the cathode, exclusively and simultaneously.
 In this exploratory R21, we propose a novel mechanism of bioelectrical control in pathogenic bacterial
targeting. Our central hypothesis is that an active epithelial “battery” exists around the FAE, which is
intrinsically exploited by bacterial pathogens for invasive targeting. We will test our hypothesis through the
following specific aims: 1) Spatially define and characterize bioelectrical activities at gut epithelia. Using
advanced electrophysiological techniques, we will measure and pharmacologically manipulate ionic current
density, trans-epithelial potential, and transmembrane potential in FAE and surrounding villus epithelium in an
ex vivo mouse cecum model. Successful completion will establish the first bioelectricity profile of intestinal
epithelium. 2) Dissect the mechanisms of bioelectricity at gut epithelia in bacterial invasive targeting. Our
working hypothesis is that enteric pathogens utilize local bioelectricity to strategically target the FAE depending
on the surface electrical properties of the bacteria. This will be tested genetically and affirmed in vitro and...

## Key facts

- **NIH application ID:** 10435567
- **Project number:** 5R21AI156409-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Yaohui Sun
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $196,250
- **Award type:** 5
- **Project period:** 2021-06-21 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10435567

## Citation

> US National Institutes of Health, RePORTER application 10435567, Bioelectricity in Gut Epithelium Drives Pathogenic Bacterial Targeting (5R21AI156409-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10435567. Licensed CC0.

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