# Structural and functional investigations of bacterial fibrillar adhesins

> **NIH NIH R35** · WASHINGTON UNIVERSITY · 2024 · $388,750

## Abstract

PROJECT SUMMARY
The ability of bacteria to adhere to each other and both biotic and abiotic surfaces is key to their ability to cause
infection and persist in the environment. Bacteria can adhere using proteinaceous adhesins, including fibrillar
adhesins. Key characteristics of fibrillar adhesins include: (i) they are extracellular, surface-associated proteins,
(ii) they possess an adhesive domain as well as a repetitive stalk domain, and (iii) they are either a monomer or
homotrimer (i.e., identical, coiled-coil) of a high molecular weight protein. Fibrillar adhesins are widely abundant
in bacteria with at least 26% of all UniProt bacterial reference proteomes containing predicted fibrillar adhesin-
like proteins. They provide a range of functionalities to the bacterial surface including adherence to host tissues,
and in many instances, fibrillar adhesins are key to structuring biofilms, which are aggregated bacterial
communities that cause chronic, difficult-to-treat infections. Thus, strategies to block fibrillar adhesin-mediated
bacterial adhesion and biofilm formation are desirable therapeutic targets. However, despite the wide-abundance
and prominent role in infection that fibrillar adhesins play, we have limited understanding of fibrillar adhesins
because their massive size and repetitive sequences have prevented structural and molecular biophysical
studies of full-length, intact proteins. Instead, structures and biomolecular interactions of well-behaving domains
of some fibrillar adhesins have been determined, and in a handful of cases, the domain structures have been
stitched together with a heavy reliance on homology modeling. The lack of structural insight into fibrillar adhesins
is problematic because protein structure is directly related to function. As it currently stands, the field lacks key
understanding of a widely used mechanism of bacterial attachment, and we are missing out on opportunities to
rationally design therapeutics to prevent bacterial attachment to abiotic and biotic surfaces and biofilm formation.
To address this knowledge gap, we will develop novel approaches to elucidate the structure and interactions of
a model fibrillar adhesin, the Pseudomonas aeruginosa biofilm matrix protein called CdrA, and then explore the
impact of these features on fibrillar adhesin function. The MIRA award will enable the PI (Reichhardt) to dedicate
greater time and resources to addressing this knowledge gap as well as training and mentoring a diverse group
of scientists at the interface between molecular biophysics and microbiology. Looking to the future, this proposed
research will open the path to the structural and molecular biophysical studies of other fibrillar adhesins as well
as other high molecular weight or repetitive proteins (e.g., eukaryotic extracellular matrix proteins).

## Key facts

- **NIH application ID:** 10941939
- **Project number:** 1R35GM155188-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Courtney Reichhardt
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $388,750
- **Award type:** 1
- **Project period:** 2024-07-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10941939

## Citation

> US National Institutes of Health, RePORTER application 10941939, Structural and functional investigations of bacterial fibrillar adhesins (1R35GM155188-01). Retrieved via AI Analytics 2026-08-20 from https://api.ai-analytics.org/grant/nih/10941939. Licensed CC0.

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