The ubiquitous human skin commensal Staphylococcus hominis protects against opportunistic pathogens

Staphylococcus hominis is frequently isolated from human skin and we hypothesize that it may protect the cutaneous barrier from opportunistic pathogens. We determined that S. hominis makes six unique auto inducing peptide (AIP) signals that inhibit the major virulence factor accessory gene regulator (agr) quorum sensing system of Staphylococcus aureus. We solved and confirmed the structures of three novel AIP signals in conditioned media by mass spectrometry, then validated synthetic AIP activity against all S. aureus agr classes. Synthetic AIPs also inhibited the conserved agr system in a related species, Staphylococcus epidermidis. We determined the distribution of S. hominis agr types on healthy human skin and found S. hominis agr-I and agr-II were highly represented across subjects. Further, synthetic AIP-II was protective in vivo against S. aureus-associated dermonecrotic or epicutaneous injury. Together, these findings demonstrate that a ubiquitous colonizer of human skin has a fundamentally protective role against opportunistic damage. Overall design: We analyzed bacterial RNA from Staphylococcus hominis (strain C5) treated for 8 hours with DMSO (vehicle) or the AgrA inhibitor Apicidin (Parlet. Et al. Cell Rep. 2019) to determine genes under the transcriptional regulation of AgrA. Each group (treatment or control) contains three biological replicates for a total of 6 samples.