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

Alan M O'Neill,Fengwu Li,Teruaki Nakatsuji,Gayathri Kalla,David J Gonzalez,Richard L Gallo,Joyce Y Cheng,Robert H Mills,Jacqueline M Norris,Nikhil Kulkarni,Joe Pogliano,Dominic Mcgrosso,Kate A Worthing,Kit Pogliano

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.

Highlights

Skin is colonized by hundreds of diverse bacterial species that exist within a complex and dynamic chemical landscape
We sought to determine whether commensal staphylococci collected from the skin, nasal, oral and perineal sites of companion dogs and cats exhibit antimicrobial activity against methicillin-resistant S. pseudintermedius (MRSP) ST71 (Figure 1A) (Ma et al, 2020; K. 100 Worthing et al, 2018)
Application were more similar to the control group, suggesting that the S. felis bacteria successfully colonized and outcompeted S. pseudintermedius ST71 on the skin (Figure 6E). To further test S. felis C4 extract as an anti-MRSP intervention, we evaluated its efficacy in limiting deep tissue infection by S. pseudintermedius injected into the dermis. 1 h after an intradermal injection of 1 x 107 CFU S. pseudintermedius ST71, two intradermal inoculations 311 of 250 μg of S. felis C4 extract were administered adjacent to the infection site

Summary

21 ABSTRACT

Methicillin-resistant Staphylococcus pseudintermedius (MRSP) is an important emerging zoonotic pathogen that causes severe skin infections. 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. 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

INTRODUCTION

318 DISCUSSION

443 MATERIALS AND METHODS

777 ACKNOWLEDGEMENTS

Findings

Specia on valida on MALDI