Metabolites derived from bacterial isolates of the human skin microbiome inhibit Staphylococcus aureus biofilm formation

The human skin microbiome is a diverse microbial ecosystem with an established role in preventing bacterial infections by producing small molecules and peptides that inhibit the growth and virulence of human bacterial pathogens. Staphylococcus aureus is a major human pathogen responsible for human diseases, ranging from acute skin and soft tissue infections to life-threatening septicemia. The ability of S. aureus to form biofilms on biotic and abiotic surfaces is a key virulence factor contributing to its success as a pathogen and increased antimicrobial resistance. The limited availability of effective antibiotics creates an urgent need to explore the human skin microbiome for therapeutically viable compounds capable of combatting S. aureus infections. Here, we investigated the ability of bacterial skin commensals to produce molecules that inhibit S. aureus biofilm formation. Using MALDI-TOF analysis, 77 human skin microbiome bacterial isolates, from the Staphylococcus and Bacillus genera, were identified. Metabolites from the cell-free concentrated media (CFCM) obtained from 26 representative isolates were evaluated for their activity on biofilm formation by both methicillin-resistant (MRSA) and methicillin-sensitive S. aureus (MSSA) strains in 96-well plate biofilm inhibition assays. CFCM derived from most of our bacterial isolates demonstrated significant inhibition of biofilm formation to varying extents, while not affecting S. aureus planktonic growth. These findings indicate that several bacterial constituents of the human skin microbiome may serve as novel sources of therapeutic agents against S. aureus -biofilm- associated infections.