TY - JOUR
T1 - The rumen microbiome: an underexplored resource for novel antimicrobial discovery
AU - Oyama, Linda
AU - Girdwood, Susan
AU - Cookson, Alan
AU - Fernandez-Fuentes, Narcis
AU - Prive, Florence
AU - Vallin, Hannah
AU - Wilkinson, Toby
AU - Golyshin, Peter
AU - Golyshina, Olga
AU - Mikut, Ralf
AU - Hilpert, Kai
AU - Richards, J
AU - Mandy, Wooton
AU - Edwards, Joan
AU - Marcesa, Marc
AU - Perrier, J
AU - Lundy, Fionnuala
AU - Luo, Y
AU - Zhou, M
AU - Hess, Matthias
AU - Mantovani, Hilario
AU - Creevey, Chris
AU - Huws, Sharon
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
U2 - 10.1038/s41522-017-0042-1
DO - 10.1038/s41522-017-0042-1
M3 - Article
VL - 3
SP - 1
EP - 10
JO - NPJ Biofilms and Microbiomes
JF - NPJ Biofilms and Microbiomes
IS - 33
ER -