# cdG Signaling and Adhesion Deployment During Biofilm Initiation

> **NIH NIH R01** · DARTMOUTH COLLEGE · 2022 · $402,252

## Abstract

Abstract:
We study the molecular mechanisms and signaling, from environmental input to physiological
output, that control bacterial biofilm formation, a key bacterial lifestyle linked to host-microbe
interactions and infectious disease. In particular, the capability of bacteria to sense and respond
to various microenvironments, particularly during the transition from a free-swimming to a
sessile biofilm lifestyle, contributes to the establishment of chronic infections. The underlying
mechanisms are equally important for non-pathogenic bacteria that can live in commensal
relationship with their host(s). Understanding the architecture and regulation of signaling
systems that control bacterial cell adhesion and biofilm formation is critical in the development
of novel therapies and preventative interventions, while providing fundamental insight into
bacterial signaling processes. Here, we propose mechanistic studies on a broadly conserved
cell adhesion system that is crucial for biofilm formation in a variety of pathogenic and
commensal organisms. We will focus on fundamental unanswered questions concerning how
cyclic-di-GMP networks control localization of these adhesins as well as how two such adhesins
contribute to formation of biofilms. We will also enhance the impact of our studies by
investigating a newly identified, analogous signaling system in an important commensal sulfate-
reducing bacterium. The central hypothesis of this proposal is that cyclic-di-GMP signaling
via a network of ligand-responsive DGCs regulates biofilm formation across a number of
microbes of importance in pathogenic, host-associated, and environmental contexts. We
propose the following Specific Aims to test this hypothesis:
 AIM 1. Test the hypothesis that small-molecule ligands are critical for regulating the localized
 cdG network via receptor complexes in P. fluorescens.
 AIM 2. Test the hypothesis that discrete domain structures of LapA and MapA in Pfl contribute
 to their differential impacts on biofilm formation.
 AIM 3. Test the hypothesis that the sulfate-reducing bacterium LapD/LapG-like system
 controls localization of this intestinal bacterium’s LapA homolog.

## Key facts

- **NIH application ID:** 10417364
- **Project number:** 1R01AI168017-01
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** George A. O'Toole
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $402,252
- **Award type:** 1
- **Project period:** 2022-03-25 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10417364

## Citation

> US National Institutes of Health, RePORTER application 10417364, cdG Signaling and Adhesion Deployment During Biofilm Initiation (1R01AI168017-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10417364. Licensed CC0.

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