In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus

Authors Organisations
  • Linda B. Oyama(Author)
    Queen's University Belfast
  • Hamza Olleik(Author)
    Université de Technologie de Compiègne, Sorbonne Universités
  • Ana Carolina Nery Teixeira(Author)
    Universidade Federal de Viçosa
  • Matheus M. Guidini(Author)
    Universidade Federal de Viçosa
  • James A. Pickup(Author)
    Queen's University Belfast
  • Brandon Yeo Pei Hui(Author)
    University College Fairview (UCF), 4178, Jalan 1/27D, Section 6, Wangsa Maju, Kuala Lumpur, 53300, Malaysia
  • Nicolas Vidal(Author)
    Aix-Marseille University
  • Alan Cookson(Author)
  • Hannah Vallin(Author)
  • Toby Wilkinson(Author)
    University of Edinburgh
  • Denise M. S. Bazzolli(Author)
    Universidade Federal de Viçosa
  • Jennifer Richards(Author)
    University Hospital of Wales
  • Mandy Wootton(Author)
    University Hospital of Wales
  • Ralf Mikut(Author)
    Karlsruhe Institute of Technology
  • Kai Hilpert(Author)
    St George’s University of London
  • Marc Maresca(Author)
    Aix-Marseille University
  • Josette Perrier(Author)
    Aix-Marseille University
  • Matthias Hess(Author)
    UC Davis
  • Hilario C. Mantovani(Author)
    Universidade Federal de Viçosa
  • Narcis Fernandez Fuentes(Author)
  • Christopher J. Creevey(Author)
    Queen's University Belfast
  • Sharon A. Huws(Author)
    Queen's University Belfast
Type Article
Original languageEnglish
Article number58
Number of pages14
Journalnpj Biofilms and Microbiomes
Volume8
Issue number1
Early online date14 Jul 2022
DOI
Publication statusPublished - 01 Dec 2022
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Abstract

Here we report two antimicrobial peptides (AMPs), HG2 and HG4 identified from a rumen microbiome metagenomic dataset, with activity against multidrug-resistant (MDR) bacteria, especially methicillin-resistant Staphylococcus aureus (MRSA) strains, a major hospital and community-acquired pathogen. We employed the classifier model design to analyse, visualise, and interpret AMP activities. This approach allowed in silico discrimination of promising lead AMP candidates for experimental evaluation. The lead AMPs, HG2 and HG4, are fast-acting and show anti-biofilm and anti-inflammatory activities in vitro and demonstrated little toxicity to human primary cell lines. The peptides were effective in vivo within a Galleria mellonella model of MRSA USA300 infection. In terms of mechanism of action, HG2 and HG4 appear to interact with the cytoplasmic membrane of target cells and may inhibit other cellular processes, whilst preferentially binding to bacterial lipids over human cell lipids. Therefore, these AMPs may offer additional therapeutic templates for MDR bacterial infections.

Keywords

  • Adenosine Monophosphate/pharmacology, Animals, Anti-Bacterial Agents/pharmacology, Antimicrobial Cationic Peptides/pharmacology, Humans, Lipids/pharmacology, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Staphylococcal Infections/drug therapy, Staphylococcus aureus/metabolism

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