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

Elife. 2021 Oct 19:10:e66793. doi: 10.7554/eLife.66793.

Abstract

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.

Keywords: B. subtilis; E. coli; Staphylococcus aureus; antimicrobial; human; infection; infectious disease; microbiology; mouse; skin; staphylococcus felis; staphylococcus pseudintermedius.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Infective Agents / chemistry
  • Anti-Infective Agents / pharmacology*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Bacteriocins / chemistry
  • Bacteriocins / pharmacology*
  • Cats / microbiology
  • Drug Resistance, Bacterial*
  • Mass Spectrometry
  • Pore Forming Cytotoxic Proteins / chemistry
  • Pore Forming Cytotoxic Proteins / pharmacology
  • Staphylococcal Infections / microbiology
  • Staphylococcal Infections / prevention & control
  • Staphylococcal Infections / veterinary*
  • Staphylococcus / chemistry*
  • Staphylococcus / drug effects*
  • Whole Genome Sequencing

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents
  • Anti-Inflammatory Agents
  • Bacteriocins
  • Pore Forming Cytotoxic Proteins
  • micrococcin

Supplementary concepts

  • Staphylococcus felis
  • Staphylococcus pseudintermedius

Associated data

  • Dryad/10.5061/dryad/D10019