A microbiome-derived metabolite from Staphylococcus epidermidis inhibits Staphylococcus aureus biofilm formation and virulence
Staphylococcus epidermidis is a common member of the healthy skin microbiome that contributes to barrier function and protection against pathogen colonization. In contrast, Staphylococcus aureus is a major human pathogen and the leading cause of skin and soft tissue infections, owing in part to its robust biofilm-forming capacity and increasing antimicrobial resistance. We previously demonstrated…
A recently discovered metabolite derived from Staphylococcus epidermidis shows promise in inhibiting the formation of Staphylococcus aureus biofilms and reducing its virulence. S. epidermidis, a common constituent of the healthy skin microbiome, typically contributes to skin protection and barrier function. In contrast, S. aureus is a major human pathogen responsible for numerous skin and soft tissue infections, partly due to its strong biofilm-forming abilities and growing resistance to antimicrobials.
Previous research had already demonstrated that cell-free conditioned media (CFCM) produced by S. epidermidis can inhibit S. aureus biofilm formation by modifying bacterial gene expression without impacting bacterial growth. In this study, researchers sought to identify the specific metabolite responsible for this antibiofilm activity. Through bioactivity-guided fractionation of S. epidermidis CFCM, scientists pinpointed pyroglutamic acid (PCA) as the active compound.
Further testing revealed that commercially sourced PCA effectively inhibited S. aureus biofilm formation and reduced its adhesion to epithelial cells. Moreover, when tested in a murine skin infection model, PCA treatment significantly decreased disease severity, expedited wound healing, and lowered bacterial counts. To confirm the identity of the bioactive constituent, researchers utilized chromatography, nuclear magnetic resonance spectroscopy, and mass spectrometry to analyze S. epidermidis CFCM, confirming the presence of PCA as the compound responsible for its antibiofilm activity.
These findings shed light on a previously unknown mechanism by which S. epidermidis suppresses S. aureus virulence. By isolating a microbiome-derived metabolite with therapeutic potential, this research highlights the potential of microbial communities as a source of novel treatments for combating S. aureus skin infections.
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