# Structure and function of staphylococcal surface proteins involved in biofilm growth and virulence

> **NIH NIH R35** · CINCINNATI CHILDRENS HOSP MED CTR · 2024 · $401,250

## Abstract

A major focus of our laboratory is to broadly understand the molecular mechanisms by which cell wall-
anchored (CWA) proteins on the surface of Staphylococcus epidermidis and S. aureus promote biofilm
formation and virulence. Staphylococcal biofilms are highly adhesive and cohesive communities of surface-
adherent bacteria that are highly resistant to antibiotic action and host immune responses, often resulting in
recalcitrant infections. Specifically, the research will focus on the large, multi-domain CWA protein Aap from S.
epidermidis, its ortholog SasG from S. aureus, and another large S. aureus CWA protein called SasC; each of
these is known to mediate homophilic interactions that promote intercellular adhesion. Mechanisms of both
reversible self-assembly and nucleation of functional amyloid fibrils will be studied in order to identify avenues
for therapeutic intervention to prevent biofilm formation. In addition, the small, secreted S. epidermidis protein
SBP and its ortholog from S. aureus will be investigated in terms of their ability to interact with Aap (and SasG)
to facilitate assembly and potentially trigger liquid-liquid phase separation of macromolecular components in
the biofilm matrix. Finally, the S. aureus protein SasX, implicated in the spread of a recent epidemic of
methicillin-resistant S. aureus, is also cell wall-anchored but unlike the other CWA proteins is a small,
intrinsically disordered protein. SasX will be assessed for its ability to interact with other staphylococcal surface
proteins as well as keratinocyte ligands, given its demonstrated role in promoting biofilm formation as well as
facilitating adhesion to epithelial cells and nasal colonization. In addition to structural and biophysical studies of
these proteins, quantitative analysis of biofilm morphology and mechanical properties using confocal
microscopy, rheometry, and force spectroscopy will provide complementary insights in a biological context.
Over the next five years, our goal is to provide a structural and functional view of how the most important
surface proteins in S. aureus and S. epidermidis physically hold the cells together in biofilms and to understand
how those protein-protein interactions mechanically strengthen the biofilm. By understanding these interactions
at the molecular level, our goal is to identify sites of vulnerability that will allow the design of therapeutic
approaches to target the ability of these bacteria to form biofilms, rendering them susceptible to a broader
range of antimicrobial agents.

## Key facts

- **NIH application ID:** 10764964
- **Project number:** 1R35GM151986-01
- **Recipient organization:** CINCINNATI CHILDRENS HOSP MED CTR
- **Principal Investigator:** ANDREW B HERR
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $401,250
- **Award type:** 1
- **Project period:** 2024-08-01 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10764964

## Citation

> US National Institutes of Health, RePORTER application 10764964, Structure and function of staphylococcal surface proteins involved in biofilm growth and virulence (1R35GM151986-01). Retrieved via AI Analytics 2026-06-12 from https://api.ai-analytics.org/grant/nih/10764964. Licensed CC0.

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