# Surface sensing, memory, and motility control in biofilm formation

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2023 · $388,765

## Abstract

PROJECT SUMMARY
Biofilms are surface-attached microbial communities that pose a significant clinical problem, in part because
biofilm cells are highly antibiotic tolerant. Device-related biofilm infections incur costs of >1 billion dollars
annually. Moreover, lethal Pseudomonas aeruginosa biofilm infections are common in cystic fibrosis (CF) and
other respiratory diseases. A better understanding of how microbial communities form is required to prevent or
reverse biofilm formation. Our reported studies show that P. aeruginosa can detect surface contact via a
pathway requiring Type IV pili (TFP) and a membrane-bound signaling complex that generates the second
messenger cAMP. Our recent findings using cell tracking of entire communities at single-cell resolution and
combined with a cAMP reporter lead to our Central Hypothesis: Surface sensing is predicated on cAMP-TFP-
based memory, and does not occur by gradually increasing surface residence times of attached cells and their
intracellular cAMP. Rather, the surface induces phase-shifted temporal waves of intracellular cAMP levels and
TFP activity that constitute a `memory' of the surface. This memory, which is multigenerational and surprisingly
robust, allows planktonic descendants of surface-exposed cells to adapt to the surface and increase surface
cell populations orders of magnitude faster than their ancestors upon attachment. To understand this pivotal
event, we will use population-level and single-cell analyses, combined with molecular genetic approaches
within a rigorous biophysical theoretical framework, to explore the mechanistic underpinnings of these earliest
events in biofilm formation. We will (1) test the hypothesis that surface contact induces phase-shifted waves of
cAMP levels and TFP activity that encode a memory of the surface, allowing for surface adaptation that
drastically modifies behavior of cells on surfaces, (2) test the hypothesis that surface sensing is transmitted via
integrating TFP mechanical retraction, inner membrane dynamics of PilA, and the formation of an inner
membrane PilJ-PilA complex required for cAMP signaling. Upon completion of the proposed studies, we will
have established the mechanism by which P. aeruginosa senses and irreversibly attaches to a surface. Given
that irreversible attachment is the first committed step in biofilm formation, our work uncovers a key aspect of
bacterial biology.

## Key facts

- **NIH application ID:** 10546429
- **Project number:** 5R01AI143730-05
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** George A. O'Toole
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $388,765
- **Award type:** 5
- **Project period:** 2019-01-22 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10546429

## Citation

> US National Institutes of Health, RePORTER application 10546429, Surface sensing, memory, and motility control in biofilm formation (5R01AI143730-05). Retrieved via AI Analytics 2026-06-11 from https://api.ai-analytics.org/grant/nih/10546429. Licensed CC0.

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