Cell wall-binding domain of staphylococcal enzyme shows unexpected antimicrobial and antifungal activity

A cell wall–binding domain once thought to merely guide a bacterial enzyme to its target has turned out to be a weapon in its own right. Researchers studying CBD_Sp_B, an SH3b domain from the peptidoglycan hydrolase SpM23_B of Staphylococcus pettenkoferi, report that the domain on its own kills bacteria — and, unexpectedly, also inhibits fungi, including Candida auris, a pathogen the World Health Organization classifies as critical priority.

Bacterial peptidoglycan hydrolases degrade the peptidoglycan layer of bacterial cell walls and are essential for cell wall remodeling during growth, division and turnover. These enzymes typically combine an enzymatically active domain with a cell wall–binding domain, and SH3b domains have been widely regarded as surface-targeting modules that enhance the activity and specificity of the full enzyme. The potential antimicrobial functions of SH3b domains independent of a catalytic partner had remained largely unexplored, which is what prompted the team to test CBD_Sp_B in isolation.

In their experiments, the domain showed potent bactericidal activity against all tested bacterial strains. The antifungal result was the surprise: activity extended to multiple Candida species, including C. auris. Electron microscopy revealed pronounced ultrastructural alterations in both bacterial and fungal cells following treatment, suggesting that the domain disrupts cellular architecture in a way that is visible at the structural level.

The mechanism appears to involve the bacterial membrane: SYTOX Green assays showed no significant membrane permeabilization, while DiSC3(5) measurements indicated a loss of membrane potential, pointing to depolarization as a component of the domain's antimicrobial activity. SYTOX Green assays showed no significant membrane permeabilization, meaning the domain does not simply punch holes that let molecules flood in. However, DiSC3(5) measurements demonstrated a loss of bacterial membrane potential, indicating that membrane depolarization is a component of the domain’s antimicrobial activity. Further analysis identified the C-terminal region of CBD_Sp_B as a key determinant of this function, pointing to a specific part of the protein that could be targeted in future engineering efforts.

There is an important catch. This limitation restricts immediate applications, although the authors note that the finding provides a basis for engineering salt-tolerant derivatives.

For now, the researchers position CBD_Sp_B as a potential novel antimicrobial scaffold, particularly for topical and non-clinical applications under low-ionic-strength conditions.

Subject of Research: Antimicrobial activity of the SH3b cell wall–binding domain of the SpM23_B peptidoglycan hydrolase

Article Title: The SH3b cell wall–binding domain of SpM23_B peptidoglycan hydrolase has antimicrobial activity

Article References: Kaus-Drobek, M., Nowacka, M., Gewartowska, M., Korzeniowska née Wiweger, M., Janeczko, M., Mitkowski, P., Stefańska, J., & Sabała, I. (2026). The SH3b cell wall–binding domain of SpM23_B peptidoglycan hydrolase has antimicrobial activity. BMC Biology. https://doi.org/10.1186/s12915-026-02773-7

Image Credits: AI Generated

DOI: 10.1186/s12915-026-02773-7

Keywords: SH3b domain, peptidoglycan hydrolase, CBD_Sp_B, Staphylococcus pettenkoferi, antimicrobial activity, antifungal activity, Candida auris, membrane depolarization, cell wall binding, BMC Biology, SH3b, cell