# Vibrio cholerae c-diGMP signaling: Motile to biofilm transition and transmission

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA CRUZ · 2021 · $772,840

## Abstract

PROJECT SUMMARY
Vibrio cholerae causes the disease cholera, an important public health problem worldwide. V. cholerae’s ability
to cause epidemics is tied to its dissemination and survival in aquatic habitats and its transmission to the human
host. The pathogen’s ability to form biofilms (i.e., matrix-enclosed, surface-associated communities) is crucial for
its survival in aquatic habitats between epidemics and is advantageous for host-to-host transmission during
epidemics. The signaling nucleotide cyclic dimeric guanosine monophosphate (c-diGMP) is broadly conserved
in bacteria and is a key regulator of biofilm formation. Understanding of how c-diGMP controls biofilm formation,
which environmental signals modulate c-diGMP levels and biofilm formation, and consequences of c-diGMP
signaling in V. cholerae infectivity, transmission and dissemination, is limited. These information gaps will
addressed by focusing on two specific aims. 1) Analyze c-diGMP signaling pathways that control biofilm
formation dynamics; and 2) Analyze activation of c-diGMP signaling pathways and their consequences in V.
cholerae infection cycle. Under the first aim, the molecular mechanism(s) through which c-diGMP controls
production of the type IVa MSHA pilus, the primary component of initial surface attachment will be determined
using structural and biochemical approaches. The down-stream c-diGMP signaling pathways initiated upon
surface attachment will be analyzed by employing microscopy-based community tracking methods to measure
motility, division, and second messenger signal levels. The mechanism by which specific key c-diGMP signaling
proteins act to control surface attachment and biofilm matrix production will be determined using combination of
genetic and biochemical approaches. Under the second aim, the mechanism of activation of key c-diGMP
signaling proteins will be determined using structural and ligand binding studies. The role of c-diGMP signaling
in in vivo biofilm formation, in V. cholerae transmission and dissemination will also be investigated, using state-
of-the-art imaging tools and novel c-diGMP sensors. The proposed work will greatly advance the understanding
of how c-diGMP signaling operates, identify the inputs that influence c-diGMP production and degradation, and
unveil the biological consequences of c-diGMP signaling. The proposed work promises molecular/mechanistic
insights that will allow us to devise ways to control c-di-GMP signal transduction pathways governing motility and
biofilm formation, ultimately providing targets for the development of inhibitors of V. cholerae transmission.

## Key facts

- **NIH application ID:** 10168435
- **Project number:** 5R01AI102584-08
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA CRUZ
- **Principal Investigator:** Havva Fitnat Yildiz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $772,840
- **Award type:** 5
- **Project period:** 2012-09-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10168435

## Citation

> US National Institutes of Health, RePORTER application 10168435, Vibrio cholerae c-diGMP signaling: Motile to biofilm transition and transmission (5R01AI102584-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10168435. Licensed CC0.

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