Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius.
Alan M O'NeillKate A WorthingNikhil KulkarniFengwu LiTeruaki NakatsujiDominic McGrossoRobert H MillsGayathri KallaJoyce Y ChengJacqueline M NorrisKit PoglianoJoe PoglianoDavid J GonzalezRichard L GalloPublished in: eLife (2021)
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.
Keyphrases
- drug resistant
- staphylococcus aureus
- multidrug resistant
- soft tissue
- acinetobacter baumannii
- wound healing
- gram negative
- mass spectrometry
- single cell
- biofilm formation
- stem cells
- oxidative stress
- cell therapy
- electron microscopy
- methicillin resistant staphylococcus aureus
- type diabetes
- mesenchymal stem cells
- escherichia coli
- cystic fibrosis
- pseudomonas aeruginosa
- high resolution
- adipose tissue
- deep learning
- insulin resistance
- antimicrobial resistance
- resting state