# Vibrio cholerae antinitrosative stress defenses and gut microbiome interaction

> **NIH NIH R01** · UNIVERSITY OF PENNSYLVANIA · 2020 · $817,177

## Abstract

PROJECT SUMMARY
The human pathogen Vibrio cholerae is the etiologic agent of the severe diarrheal disease known as cholera,
which affects millions of people annually, worldwide. In order for V. cholerae to successfully colonize in the
small intestines of the host, it must express a series of virulence factors, which have been the main focus of
the cholera research. However, bacterial pathogenicity is a multifactorial process in vivo that depends not only
on virulence factor expression, but host responses to infection and interactions with the commensal microbes
of the gut, the gut microbiome. One major set of host-produced factors that must be overcome by V. cholerae
comprises nitric oxide (NO) and NO-derived nitrogen oxides and dinitrosyl-iron complexes, collectively known
as nitrosative stress (reactive nitrogen species, RNS). Previous studies show that inducible nitric oxide
synthase (iNOS or NOS2), the enzyme that synthesizes NO, is among the most upregulated proteins in
duodenal tissue during cholera, and our results show both that iNOS is highly induced upon V. cholerae
infection of an adult mouse model, and that V. cholerae colonization is reduced in iNOS-/- mice or mice treated
with the iNOS inhibitor aminoguanidine (AG). However, little is known about how increased RNS in vivo
impacts V. cholerae, the gut microbiome, and the inter-microbial interactions that drive the ultimate outcome of
infection. We hypothesize that RNS production induced during infection modulates the structure, function, and
pathogen interactions of the gut microbiome, granting V. cholerae a competitive advantage over commensals
due to several RNS-resistance mechanisms that are tightly regulated alongside virulence factor expression.
We will examine this hypothesis in two aims. In Aim 1, we will elucidate how V. cholerae responds to RNS
during infection, and how these responses are regulated alongside virulence. In Aim 2, we will examine the
role of RNS in modulating the gut microbiome, how RNS-dependent changes influences V. cholerae
susceptibility, and how RNS affects specific microbial interactions between this pathogen and commensal gut
microbes.

## Key facts

- **NIH application ID:** 10141759
- **Project number:** 1R01AI157106-01
- **Recipient organization:** UNIVERSITY OF PENNSYLVANIA
- **Principal Investigator:** Ansel Hsiao
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $817,177
- **Award type:** 1
- **Project period:** 2020-09-23 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10141759

## Citation

> US National Institutes of Health, RePORTER application 10141759, Vibrio cholerae antinitrosative stress defenses and gut microbiome interaction (1R01AI157106-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10141759. Licensed CC0.

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