The rumen microbiome: an underexplored resource for novel antimicrobial discovery
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , , , , , , |
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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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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info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
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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eng |
dc.relation.ispartofseries.pt-BR.fl_str_mv |
3(33), Dec. 2017 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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NPJ Biofilms and Microbiomes |
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NPJ Biofilms and Microbiomes |
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