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

Abstract

S. pseudintermedius is an important emerging zoonotic pathogen that can cause skin and soft tissue infections in dogs and humans. S. pseudintermedius contains virulence and antimicrobial resistance mechanisms similar to S. aureus. To combat the increasing incidence of bacterial drug resistance, the application and transplantation of commensal antimicrobial bacteria as a bacteriotherapeutic has shown clinical promise. Here we screened a selection of staphylococci isolates collected from the skin, nasal and perineum of domestic dogs and cats for antimicrobial activity against methicillin-resistant S. pseudintermedius (MRSP). We identified a S. felis C4 isolate from feline skin that inhibited growth of several important gram-positive pathogens. S. felis C4 was suitable as a bacteriotherapy, showing sensitivity to common antibiotics and was well tolerated on mouse skin. Competition experiments in mice showed that a S. felis C4 significantly reduced MRSP colonization on mouse skin (p>0.0263). Furthermore, an antimicrobial extract from S. felis C4 supernatant significantly reduced dermonecrotic skin injury during MRSP intradermal infection (p>0.0145). Through fluorescence and electron microscopy, S. felis C4 extract disrupted bacterial cell membranes but not eukaryotic cells. LC/MS identified several phenol soluble modulin beta (PSMβ1-3) peptides made by S. felis that exhibited antimicrobial activity against MRSP. RNA-Seq analysis demonstrated that the extract and PSMβ peptides also exhibited anti-inflammatory activity, suppressing TLR-mediated cytokine release from keratinocytes. Overall, these findings report antimicrobial and anti-inflammatory activity from a commensal bacterium residing on cats that could be utilized in bacteriotherapy against difficult-to-treat animal skin infections.