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

  1. Alan M O'Neill
  2. Kate A Worthing
  3. Nikhil Kulkarni
  4. Fengwu Li
  5. Teruaki Nakatsuji
  6. Dominic McGrosso
  7. Robert H Mills
  8. Gayathri Kalla
  9. Joyce Y Cheng
  10. Jacqueline M Norris
  11. Kit Pogliano
  12. Joe Pogliano
  13. David J Gonzalez
  14. Richard L Gallo  Is a corresponding author
  1. University of California San Diego, United States
  2. University of Arizona, United States
  3. University of Sydney, Australia
  4. University of California, San Diego, United States

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

The following data sets were generated

Article and author information

Author details

  1. Alan M O'Neill

    Dermatology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5892-6477
  2. Kate A Worthing

    Veterinary Medicine, University of Arizona, Arizona, United States
    Competing interests
    Kate A Worthing, Dr. Worthing is a co-inventor of technology described in this manuscript that has been disclosed to the University of California San Diego..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8713-7189
  3. Nikhil Kulkarni

    Dermatology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  4. Fengwu Li

    Dermatology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  5. Teruaki Nakatsuji

    Dermatology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  6. Dominic McGrosso

    Dermatology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  7. Robert H Mills

    Pharmacology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  8. Gayathri Kalla

    Pharmacology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  9. Joyce Y Cheng

    Dermatology, University of California San Diego, San Diego, United States
    Competing interests
    No competing interests declared.
  10. Jacqueline M Norris

    Veterinary Science, University of Sydney, Sydney, Australia
    Competing interests
    No competing interests declared.
  11. Kit Pogliano

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7868-3345
  12. Joe Pogliano

    Division of Biological Sciences, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  13. David J Gonzalez

    Department of Pharmacology, University of California, San Diego, La Jolla, United States
    Competing interests
    No competing interests declared.
  14. Richard L Gallo

    Dermatology, University of California San Diego, San Diego, United States
    For correspondence
    rgallo@health.ucsd.edu
    Competing interests
    Richard L Gallo, is a co-founder, scientific advisor, consultant and has equity in MatriSys Biosciences and is a consultant, receives income and has equity in Sente.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1401-7861

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

  1. 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

  1. Received: January 22, 2021
  2. Preprint posted: March 8, 2021 (view preprint)
  3. Accepted: October 2, 2021
  4. Accepted Manuscript published: October 19, 2021 (version 1)
  5. 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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  1. Alan M O'Neill
  2. Kate A Worthing
  3. Nikhil Kulkarni
  4. Fengwu Li
  5. Teruaki Nakatsuji
  6. Dominic McGrosso
  7. Robert H Mills
  8. Gayathri Kalla
  9. Joyce Y Cheng
  10. Jacqueline M Norris
  11. Kit Pogliano
  12. Joe Pogliano
  13. David J Gonzalez
  14. Richard L Gallo
(2021)
Antimicrobials from a feline commensal bacterium inhibit skin infection by drug-resistant S. pseudintermedius
eLife 10:e66793.
https://doi.org/10.7554/eLife.66793

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https://doi.org/10.7554/eLife.66793