The rumen microbiome: an underexplored resource for novel antimicrobial discovery

Detalhes bibliográficos
Autor(a) principal: Oyama, Linda B.
Data de Publicação: 2017
Outros Autores: Girdwood, Susan E., Cookson, Alan R., Mantovani, Hilario C., Fernandez-Fuentes, Narcis, Privé, Florence, Vallin, Hannah E., Wilkinson, Toby J., Golyshin, Peter N., Golyshina, Olga V., Mikut, Ralf, Hilpert, Kai, Richards, Jennifer, Wootton, Mandy, Edwards, Joan E., Maresca, Marc, Perrier, Josette, etal.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: LOCUS Repositório Institucional da UFV
Texto Completo: http://dx.doi.org/10.1038/s41522-017-0042-1
http://www.locus.ufv.br/handle/123456789/16439
Resumo: Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against numerous bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.
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spelling Oyama, Linda B.Girdwood, Susan E.Cookson, Alan R.Mantovani, Hilario C.Fernandez-Fuentes, NarcisPrivé, FlorenceVallin, Hannah E.Wilkinson, Toby J.Golyshin, Peter N.Golyshina, Olga V.Mikut, RalfHilpert, KaiRichards, JenniferWootton, MandyEdwards, Joan E.Maresca, MarcPerrier, Josetteetal.2018-01-17T17:29:37Z2018-01-17T17:29:37Z2017-12-012055-5008http://dx.doi.org/10.1038/s41522-017-0042-1http://www.locus.ufv.br/handle/123456789/16439Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against numerous bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.engNPJ Biofilms and Microbiomes3(33), Dec. 2017The rumen microbiomeAntimicrobial discoveryThe rumen microbiome: an underexplored resource for novel antimicrobial discoveryinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfinfo:eu-repo/semantics/openAccessreponame:LOCUS Repositório Institucional da UFVinstname:Universidade Federal de Viçosa (UFV)instacron:UFVORIGINALartigo.pdfartigo.pdftexto completoapplication/pdf3398818https://locus.ufv.br//bitstream/123456789/16439/1/artigo.pdf7a65e0abbb289f97d6bc0d2dfed8fd58MD51LICENSElicense.txtlicense.txttext/plain; charset=utf-81748https://locus.ufv.br//bitstream/123456789/16439/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD52THUMBNAILartigo.pdf.jpgartigo.pdf.jpgIM Thumbnailimage/jpeg6026https://locus.ufv.br//bitstream/123456789/16439/3/artigo.pdf.jpg471c8348aff6e42be6c8b0d069eea162MD53123456789/164392018-01-17 22:00:53.122oai:locus.ufv.br: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Repositório InstitucionalPUBhttps://www.locus.ufv.br/oai/requestfabiojreis@ufv.bropendoar:21452018-01-18T01:00:53LOCUS Repositório Institucional da UFV - Universidade Federal de Viçosa (UFV)false
dc.title.en.fl_str_mv The rumen microbiome: an underexplored resource for novel antimicrobial discovery
title The rumen microbiome: an underexplored resource for novel antimicrobial discovery
spellingShingle The rumen microbiome: an underexplored resource for novel antimicrobial discovery
Oyama, Linda B.
The rumen microbiome
Antimicrobial discovery
title_short The rumen microbiome: an underexplored resource for novel antimicrobial discovery
title_full The rumen microbiome: an underexplored resource for novel antimicrobial discovery
title_fullStr The rumen microbiome: an underexplored resource for novel antimicrobial discovery
title_full_unstemmed The rumen microbiome: an underexplored resource for novel antimicrobial discovery
title_sort The rumen microbiome: an underexplored resource for novel antimicrobial discovery
author Oyama, Linda B.
author_facet Oyama, Linda B.
Girdwood, Susan E.
Cookson, Alan R.
Mantovani, Hilario C.
Fernandez-Fuentes, Narcis
Privé, Florence
Vallin, Hannah E.
Wilkinson, Toby J.
Golyshin, Peter N.
Golyshina, Olga V.
Mikut, Ralf
Hilpert, Kai
Richards, Jennifer
Wootton, Mandy
Edwards, Joan E.
Maresca, Marc
Perrier, Josette
etal.
author_role author
author2 Girdwood, Susan E.
Cookson, Alan R.
Mantovani, Hilario C.
Fernandez-Fuentes, Narcis
Privé, Florence
Vallin, Hannah E.
Wilkinson, Toby J.
Golyshin, Peter N.
Golyshina, Olga V.
Mikut, Ralf
Hilpert, Kai
Richards, Jennifer
Wootton, Mandy
Edwards, Joan E.
Maresca, Marc
Perrier, Josette
etal.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Oyama, Linda B.
Girdwood, Susan E.
Cookson, Alan R.
Mantovani, Hilario C.
Fernandez-Fuentes, Narcis
Privé, Florence
Vallin, Hannah E.
Wilkinson, Toby J.
Golyshin, Peter N.
Golyshina, Olga V.
Mikut, Ralf
Hilpert, Kai
Richards, Jennifer
Wootton, Mandy
Edwards, Joan E.
Maresca, Marc
Perrier, Josette
etal.
dc.subject.pt-BR.fl_str_mv The rumen microbiome
Antimicrobial discovery
topic The rumen microbiome
Antimicrobial discovery
description Antimicrobial peptides (AMPs) are promising drug candidates to target multi-drug resistant bacteria. The rumen microbiome presents an underexplored resource for the discovery of novel microbial enzymes and metabolites, including AMPs. Using functional screening and computational approaches, we identified 181 potentially novel AMPs from a rumen bacterial metagenome. Here, we show that three of the selected AMPs (Lynronne-1, Lynronne-2 and Lynronne-3) were effective against numerous bacterial pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). No decrease in MRSA susceptibility was observed after 25 days of sub-lethal exposure to these AMPs. The AMPs bound preferentially to bacterial membrane lipids and induced membrane permeability leading to cytoplasmic leakage. Topical administration of Lynronne-1 (10% w/v) to a mouse model of MRSA wound infection elicited a significant reduction in bacterial counts, which was comparable to treatment with 2% mupirocin ointment. Our findings indicate that the rumen microbiome may provide viable alternative antimicrobials for future therapeutic application.
publishDate 2017
dc.date.issued.fl_str_mv 2017-12-01
dc.date.accessioned.fl_str_mv 2018-01-17T17:29:37Z
dc.date.available.fl_str_mv 2018-01-17T17:29:37Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
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dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1038/s41522-017-0042-1
http://www.locus.ufv.br/handle/123456789/16439
dc.identifier.issn.none.fl_str_mv 2055-5008
identifier_str_mv 2055-5008
url http://dx.doi.org/10.1038/s41522-017-0042-1
http://www.locus.ufv.br/handle/123456789/16439
dc.language.iso.fl_str_mv eng
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dc.relation.ispartofseries.pt-BR.fl_str_mv 3(33), Dec. 2017
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publisher.none.fl_str_mv NPJ Biofilms and Microbiomes
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