# cdiGMP regulation of Biofilm Formation

> **NIH NIH R37** · DARTMOUTH COLLEGE · 2022 · $519,412

## Abstract

In the coming years, our goal is to understand how motile microbes, such as P. aeruginosa, regulate the
transition to a biofilm lifestyle. A key aspect of this transition is the regulation (perhaps “modulation” is a
better word) of the three surface behaviors of this microbe: flagellar mediated swarming, TFP-mediated
twitching motility and EPS-dependent biofilm formation. The experiments proposed below seek to
understand the mechanism(s) underlying the coordination of these surface behaviors. An integral aspect of
this work is defining how this microbe detects surface engagement; our work on PilY1 is allowing us to
dissect one such “surface sensing” pathway. My group has already made contributions to this exciting area
of microbiology, and we will continue to do so in the come funding period by (i) completing studies
proposed in the original application and (ii) breaking open new areas of research. To address the latter, I
propose to incorporate a new formal and funded collaboration into years 6–10 of the project with Dr. Gerard
Wong at UCLA. We have already co-published five papers with a 6th paper in press at PNAS. We propose
the following studies to continue to test the central hypothesis that cdG levels are up-regulated in
response to cell-to-substratum contact, leading to reduced motility and promotion of biofilm
formation.
Aim 1. Test the hypothesis that a protein-protein interaction cascade signals from PilY1 to SadC to
modulate c-di-GMP levels.
Aim 2. Test the hypothesis that SadC coordinates swarming and twitching motility via inner
membrane complexes.
Aim 3. Test the hypothesis that stator swapping drives distinct behaviors during early attachment.
Aim 4. Test the hypothesis that modulation of flagellar- and TFP-mediated motility contributes to
the formation of polymicrobial communities.
Aim 5. Test the hypothesis that c-di-GMP signaling is required to maintain mature biofilms.
RELEVANCE (See instructions):
Bacterial biofilm-based infections are estimated to cause upwards of a billion dollars annually in increased
medical costs. The work we propose here will reveal mechanisms whereby these communities form, and
thus provide insight into how to prevent such infections.

## Key facts

- **NIH application ID:** 10447115
- **Project number:** 5R37AI083256-14
- **Recipient organization:** DARTMOUTH COLLEGE
- **Principal Investigator:** George A. O'Toole
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $519,412
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10447115

## Citation

> US National Institutes of Health, RePORTER application 10447115, cdiGMP regulation of Biofilm Formation (5R37AI083256-14). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10447115. Licensed CC0.

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