In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus
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 path...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2022-07-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-022-00320-0 |
| _version_ | 1811293720847319040 |
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| author | Linda B. Oyama Hamza Olleik Ana Carolina Nery Teixeira Matheus M. Guidini James A. Pickup Brandon Yeo Pei Hui Nicolas Vidal Alan R. Cookson Hannah Vallin Toby Wilkinson Denise M. S. Bazzolli Jennifer Richards Mandy Wootton Ralf Mikut Kai Hilpert Marc Maresca Josette Perrier Matthias Hess Hilario C. Mantovani Narcis Fernandez-Fuentes Christopher J. Creevey Sharon A. Huws |
| author_facet | Linda B. Oyama Hamza Olleik Ana Carolina Nery Teixeira Matheus M. Guidini James A. Pickup Brandon Yeo Pei Hui Nicolas Vidal Alan R. Cookson Hannah Vallin Toby Wilkinson Denise M. S. Bazzolli Jennifer Richards Mandy Wootton Ralf Mikut Kai Hilpert Marc Maresca Josette Perrier Matthias Hess Hilario C. Mantovani Narcis Fernandez-Fuentes Christopher J. Creevey Sharon A. Huws |
| author_sort | Linda B. Oyama |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-13T05:05:47Z |
| format | Article |
| id | doaj.art-c23c7ade54b24fadb7cc4ad66c299983 |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-04-13T05:05:47Z |
| publishDate | 2022-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-c23c7ade54b24fadb7cc4ad66c2999832022-12-22T03:01:11ZengNature Portfolionpj Biofilms and Microbiomes2055-50082022-07-018111410.1038/s41522-022-00320-0In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureusLinda B. Oyama0Hamza Olleik1Ana Carolina Nery Teixeira2Matheus M. Guidini3James A. Pickup4Brandon Yeo Pei Hui5Nicolas Vidal6Alan R. Cookson7Hannah Vallin8Toby Wilkinson9Denise M. S. Bazzolli10Jennifer Richards11Mandy Wootton12Ralf Mikut13Kai Hilpert14Marc Maresca15Josette Perrier16Matthias Hess17Hilario C. Mantovani18Narcis Fernandez-Fuentes19Christopher J. Creevey20Sharon A. Huws21Institute for Global Food Security, School of Biological Sciences, Queen’s University BelfastCNRS Enzyme and Cell Engineering Laboratory, Université de Technologie de Compiègne, Sorbonne UniversitésDepartamento de Microbiologia, Universidade Federal de ViçosaDepartamento de Microbiologia, Universidade Federal de ViçosaInstitute for Global Food Security, School of Biological Sciences, Queen’s University BelfastUniversity College Fairview (UCF)Yelen Analytics, Aix-Marseille University ICRInstitute of Biological Environmental and Rural Sciences, Aberystwyth UniversityInstitute of Biological Environmental and Rural Sciences, Aberystwyth UniversityThe Roslin Institute and R(D)SVS, University of EdinburghDepartamento de Microbiologia, Universidade Federal de ViçosaSpecialist Antimicrobial Chemotherapy Unit, Public Health Wales, University Hospital of Wales, Heath ParkSpecialist Antimicrobial Chemotherapy Unit, Public Health Wales, University Hospital of Wales, Heath ParkKarlsruhe Institute of Technology, Institute for Automation and Applied InformaticsInstitute of Infection and Immunity, St George’s, University of London, Cranmer TerraceAix Marseille UniversityAix Marseille UniversityUC Davis, College of Agricultural and Environmental SciencesDepartamento de Microbiologia, Universidade Federal de ViçosaInstitute of Biological Environmental and Rural Sciences, Aberystwyth UniversityInstitute for Global Food Security, School of Biological Sciences, Queen’s University BelfastInstitute for Global Food Security, School of Biological Sciences, Queen’s University BelfastAbstract 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.https://doi.org/10.1038/s41522-022-00320-0 |
| spellingShingle | Linda B. Oyama Hamza Olleik Ana Carolina Nery Teixeira Matheus M. Guidini James A. Pickup Brandon Yeo Pei Hui Nicolas Vidal Alan R. Cookson Hannah Vallin Toby Wilkinson Denise M. S. Bazzolli Jennifer Richards Mandy Wootton Ralf Mikut Kai Hilpert Marc Maresca Josette Perrier Matthias Hess Hilario C. Mantovani Narcis Fernandez-Fuentes Christopher J. Creevey Sharon A. Huws In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus npj Biofilms and Microbiomes |
| title | In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus |
| title_full | In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus |
| title_fullStr | In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus |
| title_full_unstemmed | In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus |
| title_short | In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus |
| title_sort | in silico identification of two peptides with antibacterial activity against multidrug resistant staphylococcus aureus |
| url | https://doi.org/10.1038/s41522-022-00320-0 |
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