2. Academic Validation
  3. In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus

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

  • NPJ Biofilms Microbiomes. 2022 Jul 14;8(1):58. doi: 10.1038/s41522-022-00320-0.
Linda B Oyama # 1,  Hamza Olleik # 2,  Ana Carolina Nery Teixeira 3,  Matheus M Guidini 3,  James A Pickup 4,  Brandon Yeo Pei Hui 5,  Nicolas Vidal 6,  Alan R Cookson 7,  Hannah Vallin 7,  Toby Wilkinson 8,  Denise M S Bazzolli 3,  Jennifer Richards 9,  Mandy Wootton 9,  Ralf Mikut 10,  Kai Hilpert 11,  Marc Maresca 12,  Josette Perrier 12,  Matthias Hess 13,  Hilario C Mantovani 3,  Narcis Fernandez-Fuentes 7,  Christopher J Creevey 4,  Sharon A Huws 14
Affiliations

Affiliations

  • 1 Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK. [email protected].
  • 2 CNRS Enzyme and Cell Engineering Laboratory, Université de Technologie de Compiègne, Sorbonne Universités, Rue du Docteur Schweitzer, CS 60319, CEDEX, 60203, Compiègne, France.
  • 3 Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, 36570-900, Brasil.
  • 4 Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK.
  • 5 University College Fairview (UCF), 4178, Jalan 1/27D, Section 6, Wangsa Maju, 53300, Kuala Lumpur, Malaysia.
  • 6 Yelen Analytics, Aix-Marseille University ICR, 13013, Marseille, France.
  • 7 Institute of Biological Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Wales, SY23 3DA, UK.
  • 8 The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom.
  • 9 Specialist Antimicrobial Chemotherapy Unit, Public Health Wales, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK.
  • 10 Karlsruhe Institute of Technology, Institute for Automation and Applied Informatics, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein, Leopoldshafen, Germany.
  • 11 Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK.
  • 12 Aix Marseille University, CNRS, Centrale Marseille, iSm2, Marseille, France.
  • 13 UC Davis, College of Agricultural and Environmental Sciences, California, 95616, CA, USA.
  • 14 Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK. [email protected].
  • # Contributed equally.
PMID: 35835775 DOI: 10.1038/s41522-022-00320-0
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.

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