College of Veterinary Medicine, University of Arizona, Oro Valley, United States
Nikhil Kulkarni
Department of Dermatology, University of California, San Diego, San Diego, United States
Fengwu Li
Department of Dermatology, University of California, San Diego, San Diego, United States
Teruaki Nakatsuji
Department of Dermatology, University of California, San Diego, San Diego, United States
Dominic McGrosso
Department of Pharmacology, University of California, San Diego, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United States
Robert H Mills
Department of Pharmacology, University of California, San Diego, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United States
Gayathri Kalla
Division of Biological Sciences, University of California, San Diego, San Diego, United States
Joyce Y Cheng
Department of Dermatology, University of California, San Diego, San Diego, United States
Jacqueline M Norris
Sydney School of Veterinary Science, University of Sydney, Sydney, Australia
Division of Biological Sciences, University of California, San Diego, San Diego, United States
Joe Pogliano
Division of Biological Sciences, University of California, San Diego, San Diego, United States
David J Gonzalez
Department of Pharmacology, University of California, San Diego, San Diego, United States; Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, San Diego, United States
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. Whole genome sequencing and mass spectrometry revealed several secreted antimicrobials including a thiopeptide bacteriocin micrococcin P1 and phenol-soluble modulin beta (PSMβ) peptides that exhibited antimicrobial and anti-inflammatory activity. Fluorescence and electron microscopy revealed that S. felis antimicrobials inhibited translation and disrupted bacterial but not eukaryotic cell membranes. 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. These findings indicate a feline commensal bacterium that could be utilized in bacteriotherapy against difficult-to-treat animal and human skin infections.
