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^*

^*Awdur cyfatebol y gwaith hwn

Adran y Gwyddorau Bywyd

Allbwn ymchwil: Cyfraniad at gyfnodolyn › Erthygl › adolygiad gan gymheiriaid

18 Dyfyniadau (Scopus)

131 Wedi eu Llwytho i Lawr (Pure)

Crynodeb

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.

Iaith wreiddiol	Saesneg
Rhif yr erthygl	58
Nifer y tudalennau	14
Cyfnodolyn	npj Biofilms and Microbiomes
Cyfrol	8
Rhif cyhoeddi	1
Dyddiad ar-lein cynnar	14 Gorff 2022
Dynodwyr Gwrthrych Digidol (DOIs)	https://doi.org/10.1038/s41522-022-00320-0
Statws	Cyhoeddwyd - 01 Rhag 2022

Mynediad at Ddogfen

10.1038/s41522-022-00320-0Trwydded: CC BY

ArticleFersiwn derfynol wedi’i chyhoeddi, 2.68 MBTrwydded: CC BY
Supplementary InformationFersiwn derfynol wedi’i chyhoeddi, 1.37 MBTrwydded: CC BY

Cysylltiad parhaol

Dolen barhaus

Ffeiliau eraill a chysylltiadau

3 Wedi Gorffen

BBSRC Core Strategic Programme in Resilient Crops: Grasslands Gogerddan
Armstead, I. (Prif Ymchwilydd), Donnison, I. (Cyd-ymchwilydd), Jones, H. (Cyd-ymchwilydd), Skot, L. (Cyd-ymchwilydd), Fernandez Fuentes, N. (Cyd-ymchwilydd), Phillips, D. (Prif Ymchwilydd), Kingston-Smith, A. (Cyd-ymchwilydd) & Bosch, M. (Cyd-ymchwilydd)
Biotechnology and Biological Sciences Research Council
01 Ebr 2017 → 31 Maw 2020
Prosiect: Ymchwil a ariannwyd yn allanol
Prospecting the rumen ecosystem for novel antimicrobials for animal and human health- INSTITUTIONAL LINKS
Huws, S. (Prif Ymchwilydd)
Newton fund
01 Ebr 2015 → 31 Maw 2017
Prosiect: Ymchwil a ariannwyd yn allanol
Characterisation and exploitation of novel antimicrobials within the rumen microbiota
Huws, S. (Prif Ymchwilydd), Creevey, C. (Cyd-ymchwilydd), Kingston-Smith, A. (Cyd-ymchwilydd), McEwan, N. (Cyd-ymchwilydd) & Newbold, J. (Cyd-ymchwilydd)
Biotechnology and Biological Sciences Research Council
01 Ebr 2014 → 31 Maw 2018
Prosiect: Ymchwil a ariannwyd yn allanol

Dyfynnu hyn

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), erthygl 58. https://doi.org/10.1038/s41522-022-00320-0

@article{8d4388962ce44067a261041eae464c62,

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,

day = "1",

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

language = "English",

volume = "8",

journal = "npj Biofilms and Microbiomes",

publisher = "Springer Nature",

number = "1",

}

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, cyfrol. 8, rhif 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

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

Crynodeb

Mynediad at Ddogfen

Cysylltiad parhaol

Ffeiliau eraill a chysylltiadau

Ôl bys

Prosiectau

BBSRC Core Strategic Programme in Resilient Crops: Grasslands Gogerddan

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

Characterisation and exploitation of novel antimicrobials within the rumen microbiota

Dyfynnu hyn