The rumen microbiome: an underexplored resource for novel antimicrobial discovery

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 ident...

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Detalhes bibliográficos
Autores: 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.
Formato: artículo
Estado:Versión publicada
Fecha de publicación:2017
País:Brasil
Recursos:Universidade Federal de Viçosa (UFV)
Repositorio:LOCUS Repositório Institucional da UFV
Idioma:inglés
OAI Identifier:oai:locus.ufv.br:123456789/16439
Acesso em linha:http://dx.doi.org/10.1038/s41522-017-0042-1
http://www.locus.ufv.br/handle/123456789/16439
Access Level:acceso abierto
Palavra-chave:The rumen microbiome
Antimicrobial discovery
Descrição
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.