# Environmental adaptation by Vibrio cholerae

> **NIH NIH R56** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $467,277

## Abstract

PROJECT SUMMARY/ABSTRACT
 Cholera is an acute diarrheal disease that affects 3-5 million people each year. Cholera is an is
caused by the Gram negative bacterium Vibrio cholerae and is frequently associated with epidemic
disease. V. cholerae is a native to aquatic ecosystems and a facultative human pathogen that infects
people through the consumption of contaminated water or food. Once ingested, V. cholerae colonizes the
small intestine where it produces a toxin that causes a dehydrating secretory diarrhea that can be rapidly
fatal. The devastating consequences of cholera, combined with the rapidity with which it can spread and
its ability to persist in aquatic ecosystems, underscore the need for the development of novel approaches
to combat this epidemic disease. Our recent studies in V. cholerae documented that multiple drug efflux
systems belonging to the resistance-nodulation-division (RND) superfamily function to efflux cellular
metabolites from the cell. We further showed that impaired efflux resulted in the metabolites accumulating
intracellularly where they interacted with periplasmic sensor proteins to initiate adaptive responses. This
included the activation of ToxR which resulted in increased leuO transcription and the downregulation of
virulence gene expression. However, the metabolites that were responsible for virulence repression
remain unknown. In this proposal we will test the hypothesis that auto-inducers function to initiate the
expression of the adaptive responses that resulted in virulence repression. Two specific aims are
proposed. The first aim will investigate the function of ToxR and LeuO in cell density-dependent gene
regulation. The second aim will investigate the contribution of RND-mediated efflux to adaptive responses
and colonization. Determining the regulatory mechanisms and environmental cues that modulate V.
cholerae adaptive responses will illuminate important aspects of V. cholerae pathogenesis, provide a
better understanding of the factors that contribute to disease and epidemic spread, and highlight novel
approaches to combat cholera.

## Key facts

- **NIH application ID:** 10633541
- **Project number:** 2R56AI132460-05
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JAMES Edward BINA
- **Activity code:** R56 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $467,277
- **Award type:** 2
- **Project period:** 2018-08-01 → 2023-03-05

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10633541

## Citation

> US National Institutes of Health, RePORTER application 10633541, Environmental adaptation by Vibrio cholerae (2R56AI132460-05). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10633541. Licensed CC0.

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