Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius
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.
Data availability
The RNA Sequencing data has been deposited in Dryad with a unique DOI identifier provided:doi:10.6076/D10019
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Antimicrobials from a feline skin commensal bacterium inhibit skin colonization and infection by drug-resistant S. pseudintermediusDryad Digital Repository, doi:10.6076/D10019.
Article and author information
Author details
Funding
National Institute of Diabetes and Digestive and Kidney Diseases (T32 DK007202)
- Robert H Mills
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Sophie Helaine, Harvard Medical School, United States
Ethics
Animal experimentation: All experiments involving live animal work were performed in accordance with the approval of the University of California, San Diego Institutional Animal Care and Use Guidelines (protocol no. S09074)
Version history
- Received: January 22, 2021
- Preprint posted: March 8, 2021 (view preprint)
- Accepted: October 2, 2021
- Accepted Manuscript published: October 19, 2021 (version 1)
- Version of Record published: October 21, 2021 (version 2)
Copyright
© 2021, O'Neill et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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