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

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

doi:10.1038/s41522-022-00320-0

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

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-FuentesChristopher J. Creevey, Sharon A. Huws

Department of Life Sciences

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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.

Original language	English
Article number	58
Number of pages	14
Journal	npj Biofilms and Microbiomes
Volume	8
Issue number	1
Early online date	14 Jul 2022
DOIs	https://doi.org/10.1038/s41522-022-00320-0
Publication status	Published - 01 Dec 2022

Keywords

Adenosine Monophosphate/pharmacology
Animals
Anti-Bacterial Agents/pharmacology
Antimicrobial Cationic Peptides/pharmacology
Humans
Lipids/pharmacology
Methicillin-Resistant Staphylococcus aureus
Microbial Sensitivity Tests
Staphylococcal Infections/drug therapy
Staphylococcus aureus/metabolism

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ArticleFinal published version, 2.68 MBLicence: CC BY
Supplementary InformationFinal published version, 1.37 MBLicence: CC BY

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Oyama, L. B., Olleik, H., Teixeira, A. C. N., Guidini, M. M., Pickup, J. A., Hui, B. Y. P., Vidal, N., Cookson, A. R., Vallin, H., Wilkinson, T., Bazzolli, D. M. S., Richards, J., Wootton, M., Mikut, R., Hilpert, K., Maresca, M., Perrier, J., Hess, M., Mantovani, H. C., ... Huws, S. A. (2022). In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus. npj Biofilms and Microbiomes, 8(1), [58]. https://doi.org/10.1038/s41522-022-00320-0

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title = "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 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.",

keywords = "Adenosine Monophosphate/pharmacology, Animals, Anti-Bacterial Agents/pharmacology, Antimicrobial Cationic Peptides/pharmacology, Humans, Lipids/pharmacology, Methicillin-Resistant Staphylococcus aureus, Microbial Sensitivity Tests, Staphylococcal Infections/drug therapy, Staphylococcus aureus/metabolism",

author = "Oyama, {Linda B.} and Hamza Olleik and Teixeira, {Ana Carolina Nery} and Guidini, {Matheus M.} and Pickup, {James A.} and Hui, {Brandon Yeo Pei} and Nicolas Vidal and Cookson, {Alan R.} and Hannah Vallin and Toby Wilkinson and Bazzolli, {Denise M. S.} and Jennifer Richards and Mandy Wootton and Ralf Mikut and Kai Hilpert and Marc Maresca and Josette Perrier and Matthias Hess and Mantovani, {Hilario C.} and Narcis Fernandez-Fuentes and Creevey, {Christopher J.} and Huws, {Sharon A.}",

note = "Funding Information: This project was funded partly by the Cross River State Government of Nigeria, the Life Sciences Research Network Wales, RCUK Newton Institutional Link Fund (172629373) and the BBSRC UK (BB/L026716/1). HCM and DMSB thank the support from FAPEMIG and the Coordination for the Improvement of Higher Education Personnel (CAPES) for providing the Joint Institutional Links grant. KH thanks the Institute of Infection and Immunity of St. George{\textquoteright}s University of London for a start-up grant. We are also grateful to Dr. Colin Greengrass, for his advice. Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

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doi = "10.1038/s41522-022-00320-0",

language = "English",

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Oyama, LB, Olleik, H, Teixeira, ACN, Guidini, MM, Pickup, JA, Hui, BYP, Vidal, N, Cookson, AR , Vallin, H, Wilkinson, T, Bazzolli, DMS, Richards, J, Wootton, M, Mikut, R, Hilpert, K, Maresca, M, Perrier, J, Hess, M, Mantovani, HC, Fernandez-Fuentes, N, Creevey, CJ & Huws, SA 2022, 'In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus', npj Biofilms and Microbiomes, vol. 8, no. 1, 58. https://doi.org/10.1038/s41522-022-00320-0

TY - JOUR

T1 - In silico identification of two peptides with antibacterial activity against multidrug-resistant Staphylococcus aureus

AU - Oyama, Linda B.

AU - Olleik, Hamza

AU - Teixeira, Ana Carolina Nery

AU - Guidini, Matheus M.

AU - Pickup, James A.

AU - Hui, Brandon Yeo Pei

AU - Vidal, Nicolas

AU - Cookson, Alan R.

AU - Vallin, Hannah

AU - Wilkinson, Toby

AU - Bazzolli, Denise M. S.

AU - Richards, Jennifer

AU - Wootton, Mandy

AU - Mikut, Ralf

AU - Hilpert, Kai

AU - Maresca, Marc

AU - Perrier, Josette

AU - Hess, Matthias

AU - Mantovani, Hilario C.

AU - Fernandez-Fuentes, Narcis

AU - Creevey, Christopher J.

AU - Huws, Sharon A.

N1 - Funding Information: This project was funded partly by the Cross River State Government of Nigeria, the Life Sciences Research Network Wales, RCUK Newton Institutional Link Fund (172629373) and the BBSRC UK (BB/L026716/1). HCM and DMSB thank the support from FAPEMIG and the Coordination for the Improvement of Higher Education Personnel (CAPES) for providing the Joint Institutional Links grant. KH thanks the Institute of Infection and Immunity of St. George’s University of London for a start-up grant. We are also grateful to Dr. Colin Greengrass, for his advice. Publisher Copyright: © 2022, The Author(s).

PY - 2022/12/1

Y1 - 2022/12/1

N2 - 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.

AB - 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.

KW - Adenosine Monophosphate/pharmacology

KW - Animals

KW - Anti-Bacterial Agents/pharmacology

KW - Antimicrobial Cationic Peptides/pharmacology

KW - Humans

KW - Lipids/pharmacology

KW - Methicillin-Resistant Staphylococcus aureus

KW - Microbial Sensitivity Tests

KW - Staphylococcal Infections/drug therapy

KW - Staphylococcus aureus/metabolism

UR - https://github.com/brandonyph/SaureusRNASeq

UR - http://www.scopus.com/inward/record.url?scp=85134125935&partnerID=8YFLogxK

U2 - 10.1038/s41522-022-00320-0

DO - 10.1038/s41522-022-00320-0

M3 - Article

C2 - 35835775

SN - 2055-5008

VL - 8

JO - npj Biofilms and Microbiomes

JF - npj Biofilms and Microbiomes

IS - 1

M1 - 58

ER -

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

Abstract

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Prospecting the rumen ecosystem for novel antimicrobials for animal and human health- INSTITUTIONAL LINKS

Characterisation and exploitation of novel antimicrobials within the rumen microbiota

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

Abstract

Keywords

Access to Document

Permanent link

Other files and links

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Projects

Prospecting the rumen ecosystem for novel antimicrobials for animal and human health- INSTITUTIONAL LINKS

Characterisation and exploitation of novel antimicrobials within the rumen microbiota

Cite this