In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus - Aix-Marseille Université Access content directly
Journal Articles npj Biofilms and Microbiomes Year : 2022

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

Linda B Oyama
Brandon Yeo Pei Hui
  • Function : Author
Nicolas Vidal
  • Function : Author
  • PersonId : 1214272
  • IdRef : 165157682
Alan R Cookson
  • Function : Author
Hannah Vallin
  • Function : Author
Denise M S Bazzolli
  • Function : Author
Jennifer Richards
  • Function : Author
Mandy Wootton
  • Function : Author
Ralf Mikut
Kai Hilpert
Marc Maresca
Matthias Hess
Hilario C Mantovani
  • Function : Author
Narcis Fernandez-Fuentes
Christopher J Creevey
  • Function : Author
Sharon A Huws
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  • PersonId : 1237294

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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hal-04031127 , version 1 (15-03-2023)

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Linda B Oyama, Hamza Olleik, Ana Carolina Nery Teixeira, Matheus M Guidini, James A Pickup, et al.. In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus. npj Biofilms and Microbiomes, 2022, 8 (1), pp.58. ⟨10.1038/s41522-022-00320-0⟩. ⟨hal-04031127⟩
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