Antimicrobials from a feline skin commensal bacterium inhibit skin colonization and infection by drug-resistant S. pseudintermedius

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. To combat infections from drug-resistant bacteria, the transplantation of commensal antimicrobial bacteria as a therapeutic has shown clinical promise. We screened a collection of diverse staphylococcus species from domestic dogs and cats for antimicrobial activity against MRSP. A unique strain (S. felis C4) was isolated from feline skin that inhibited MRSP and multiple gram-positive pathogens. Competition experiments in mice showed that S. felis significantly reduced MRSP skin colonization and an antimicrobial extract from S. felis significantly reduced necrotic skin injury from MRSP infection. Fluorescence and electron microscopy revealed that S. felis antimicrobials disrupted bacterial but not eukaryotic cell membranes. LC/MS identified several S. felis phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory...