Protease Regulation in Staphylococcus aureus Biofilms

Staphylococcus aureus forms biofilms—structured multicellular communities embedded in a self‐produced matrix—that underlie chronic and device‐associated infections. The formation, maturation and dispersal of these biofilms are tightly governed by the controlled production of extracellular proteases, which cleave matrix components and modulate the stability of surface proteins. Central to this regulation are global transcriptional regulators such as SarA, which represses protease gene expression to promote matrix integrity, and the agr quorum sensing system, which induces protease expression to initiate dispersal. A dynamic balance between these opposing pathways ensures biofilm development, maintenance and eventual release of cells to colonise new niches. Dysregulation of protease activity can lead to premature dispersal or excessive matrix retention, with significant consequences for infection persistence and antibiotic susceptibility. Protease regulation is therefore critical not only for S. aureus pathogenesis but also for designing strategies to prevent or disrupt biofilms on medical devices and tissues.

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Protease Regulation in Staphylococcus aureus Biofilms publication trend

The graph below shows the total number of articles in protease regulation in staphylococcus aureus biofilms across all publications each year (not limited to Nature Index journals).

Technical terms

Biofilm: A multicellular community of bacteria encased in a self‐produced extracellular matrix adhered to surfaces.

Protease: An enzyme that catalyses the breakdown of proteins by hydrolysing peptide bonds.

Extracellular protease: Proteases secreted by cells to degrade proteins outside the bacterial cytoplasm, influencing biofilm matrix and host interactions.

SarA: A global transcriptional regulator in S. aureus that represses protease gene expression to promote biofilm formation and virulence.

agr system: A quorum sensing regulatory network in S. aureus that activates expression of virulence factors, including proteases, in response to population density, facilitating biofilm dispersal.

References

1. The major role of sarA in limiting Staphylococcus aureus extracellular protease production in vitro is correlated with decreased virulence in diverse clinical isolates in osteomyelitis. Virulence (2023).
2. Quercetin targets SarA of methicillin-resistant Staphylococcus aureus to mitigate biofilm formation. Microbiology Spectrum (2023).
3. Impact of individual extracellular proteases on Staphylococcus aureus biofilm formation in diverse clinical isolates and their isogenic sarA mutants. MicrobiologyOpen (2014).
4. Epistatic Relationships between sarA and agr in Staphylococcus aureus Biofilm Formation. PLOS ONE (2010).