# Characterization of cyclic-GMP-cAMP regulation in Vibrio cholerae

> **NIH NIH R21** · UNIV OF MARYLAND, COLLEGE PARK · 2022 · $220,095

## Abstract

ABSTRACT
Vibrio cholerae is a pathogen capable of causing worldwide pandemics including seven in
the scientific record. The seventh pandemic El Tor biotype that displaced the classical
biotype responsible for the first six pandemics differ genetically by many single
nucleotide polymorphisms and the acquisition of two large genetic islands called Vibrio seventh
pandemic islands I and II (VSP-I and VSP-II). The VSP-I island encodes eleven genes,
including dncV which encodes a dinucleotide cyclase enzyme that produces the cyclic-
GMP-AMP (cGAMP) molecule. Virulence studies in the infant mice model of infection revealed
that dncV is the only gene in VSP-I, that when mutated, has a competitive disadvantage
compared to the parental strain. This provides strong evidence that DncV and cGAMP is
important for virulence. How cGAMP regulated downstream pathways to enhance virulence
remained unresolved. Recently, a study revealed that another gene in VSP-I called capV, that is
immediately adjacent to dncV, encodes a phospholipase that is activated by binding to
cGAMP. These results suggest that cGAMP acts on the cell by binding protein receptors in
a manner similar in concept of other cyclic dinucleotides. While the discover of CapV
explained the effect of DncV and cGAMP on lipid metabolism in V. cholerae, the effect of
cGAMP on virulence, MSHA expression and chemotaxis expression are unexplained. This
proposal hypothesizes that additional protein receptor(s) bind directly to cGAMP to mediate
downstream regulation of MSHA, chemotaxis and pathogenesis. We will test our hypothesis
by using biochemical and genetic approaches including: Aim 1. Identifying interacting
proteins of cGAMP and Aim 2. Characterizing cGAMP down regulation of the MSHA
operons. Together, results from the completion of this aim will reveal how cGAMP signaling
occurs in V. cholerae and shed light on the intersection between cGAMP and cyclic-di-GMP
(c-di-GMP), another cyclic dinucleotide molecule also used by V. cholerae. In addition,
revealing the network of signaling molecules in V. cholerae will allow better understand of
pathogens can adapt when they acquire cGAMP signaling via horizontal gene transfer.

## Key facts

- **NIH application ID:** 10371521
- **Project number:** 1R21AI159467-01A1
- **Recipient organization:** UNIV OF MARYLAND, COLLEGE PARK
- **Principal Investigator:** VINCENT T LEE
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $220,095
- **Award type:** 1
- **Project period:** 2022-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371521

## Citation

> US National Institutes of Health, RePORTER application 10371521, Characterization of cyclic-GMP-cAMP regulation in Vibrio cholerae (1R21AI159467-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10371521. Licensed CC0.

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