The rumen microbiome: an underexplored resource for novel antimicrobial discovery

Abstract

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.

Addressing Global Ruminant Agricultural Challenges Through Understanding the Rumen Microbiome: Past, Present, and Future

“…Subsequently, metagenomics has been used to study many aspects of rumen microbiology, including methane emissions in cattle (Wallace et al, 2015 ) and sheep (Shi et al, 2014 ), biomarkers to predict ruminal methanogenesis (Auffret et al, 2017b ), the effect of feed-conversion-ratio, and breed and host genetics on the composition of the rumen microbiome (Roehe et al, 2016 ), nutrient acquisition (Mayorga et al, 2016 ; Rubino et al, 2017 ), and effects of diet (Auffret et al, 2017a , b ), and investigate impact of feed additives (Thomas et al, 2017 ) on the abundance of antimicrobial-resistance genes. The rumen also remains a source of valuable bioactives for the biotechnology industry, and metagenomics is a key tool for such bioprospecting (Oyama et al, 2017 ; Roumpeka et al, 2017 ). More recently, metagenomic sequences have also resulted in an enhanced understanding of niche specialization within rumen bacteria (Rubino et al, 2017 ).…”

Extensive Unexplored Human Microbiome Diversity Revealed by Over 150,000 Genomes from Metagenomes Spanning Age, Geography, and Lifestyle

“…Here, we present a set of 154,723 microbial genomes that are often prevalent, population specific, and/or geographically specific that we reconstructed via single-sample assembly from a total of 9,428 global, body-wide metagenomes. Other studies have also succeeded in reconstructing microbial genomes by metagenomic assembly on single human cohorts ( Bäckhed et al., 2015 , Brooks et al., 2017 , Ferretti et al., 2018 , Human Microbiome Project Consortium, 2012 , Raveh-Sadka et al., 2015 , Sharon et al., 2013 ), but systematic cross-study cataloging of metagenomically assembled genomes focused so far on non-human environments ( Oyama et al., 2017 , Parks et al., 2017 ). Complementary techniques, such as co-abundance of gene groups ( Nielsen et al., 2014 ), can identify genomic bins without reference, but these techniques do not account for sample-specific strains and strain-level differences in the sequence reconstruction and thus require downstream single-nucleotide variation analysis on specific genomic regions to uncover strain variability ( Quince et al., 2017b , Truong et al., 2017 ).…”

2018 Abstracts

“…The pathogen was allowed to reach 1 × 10-6 cells/ml before a challenge with novel antimicrobial peptides (AMPs) was performed. All of the AMPs were added at a concentration of 1024 mg/L, the AMPs were derived from the rumen microbiome (Oyama et al, 2017). The concentration of the pathogen was determined using a Haemocytometer post-staining with 0.4% trypan blue, and the cells were counted at 40 X magnification.…”