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

Autor: Oyama LB; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK. l.oyama@qub.ac.uk., Olleik H; CNRS Enzyme and Cell Engineering Laboratory, Université de Technologie de Compiègne, Sorbonne Universités, Rue du Docteur Schweitzer, CS 60319, CEDEX, 60203, Compiègne, France., Teixeira ACN; Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, 36570-900, Brasil., Guidini MM; Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, 36570-900, Brasil., Pickup JA; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK., Hui BYP; University College Fairview (UCF), 4178, Jalan 1/27D, Section 6, Wangsa Maju, 53300, Kuala Lumpur, Malaysia., Vidal N; Yelen Analytics, Aix-Marseille University ICR, 13013, Marseille, France., Cookson AR; Institute of Biological Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Wales, SY23 3DA, UK., Vallin H; Institute of Biological Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Wales, SY23 3DA, UK., Wilkinson T; The Roslin Institute and R(D)SVS, University of Edinburgh, Edinburgh, United Kingdom., Bazzolli DMS; Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, 36570-900, Brasil., Richards J; Specialist Antimicrobial Chemotherapy Unit, Public Health Wales, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK., Wootton M; Specialist Antimicrobial Chemotherapy Unit, Public Health Wales, University Hospital of Wales, Heath Park, Cardiff, CF14 4XW, UK., Mikut R; Karlsruhe Institute of Technology, Institute for Automation and Applied Informatics, Hermann-von-Helmholtz-Platz 1, 76344, Eggenstein, Leopoldshafen, Germany., Hilpert K; Institute of Infection and Immunity, St George's, University of London, Cranmer Terrace, London, SW17 0RE, UK., Maresca M; Aix Marseille University, CNRS, Centrale Marseille, iSm2, Marseille, France., Perrier J; Aix Marseille University, CNRS, Centrale Marseille, iSm2, Marseille, France., Hess M; UC Davis, College of Agricultural and Environmental Sciences, California, 95616, CA, USA., Mantovani HC; Departamento de Microbiologia, Universidade Federal de Viçosa, Viçosa, 36570-900, Brasil., Fernandez-Fuentes N; Institute of Biological Environmental and Rural Sciences, Aberystwyth University, Aberystwyth, Wales, SY23 3DA, UK., Creevey CJ; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK., Huws SA; Institute for Global Food Security, School of Biological Sciences, Queen's University Belfast, 19 Chlorine Gardens, Belfast, Northern Ireland, BT9 5DL, UK. s.huws@qub.ac.uk.
Jazyk: angličtina
Zdroj: NPJ biofilms and microbiomes [NPJ Biofilms Microbiomes] 2022 Jul 14; Vol. 8 (1), pp. 58. Date of Electronic Publication: 2022 Jul 14.
DOI: 10.1038/s41522-022-00320-0
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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