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

• DOI: 10.1038/s41522-022-00320-0
• Publication Date: 2022-07-14T13:03:49Z
• Authors: Linda B. Oyama; Hamza Olleik; Ana Carolina Nery...; Matheus M. Guidini; James A. Pickup; Brandon Yeo Pei Hui; Nicolas Vidal; Alan R. Cookson; Hannah Vallin; Toby Wilkinson; Denise M. S. Bazz...; Jennifer Richards; Mandy Wootton; Ralf Mikut; Kai Hilpert; Marc Maresca; Josette Perrier; Matthias Hess; Hilario C. Mantovani; Narcis Fernandez-...; Christopher J. Cr...; Sharon A. Huws
• Keywords: Human pathogen

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, major hospital community-acquired pathogen. We employed the classifier model design to analyse, visualise, interpret AMP activities. This approach allowed in silico discrimination of promising lead candidates for experimental evaluation. The AMPs, HG4, are fast-acting show anti-biofilm anti-inflammatory activities vitro demonstrated little toxicity human primary cell lines. were effective vivo within Galleria mellonella MRSA USA300 infection. In terms mechanism action, appear interact cytoplasmic membrane target cells may inhibit other cellular processes, whilst preferentially binding bacterial lipids over lipids. Therefore, these AMPs offer additional therapeutic templates MDR infections.