The rumen microbiome: an underexplored resource for novel antimicrobial discovery

The rumen microbiome: an underexplored resource for novel antimicrobial discovery
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瘤胃微生物组:新型抗菌药物发现的尚未开发的资源

DOI:
10.1101/148221
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发表时间:
2017
期刊:
--
影响因子:
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通讯作者:
Oyama L
Oyama L
中科院分区:
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作者:
Oyama L

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抗菌肽(Antimicrobial peptides,AMP)是一种很有前途的靶向治疗多重耐药菌的候选药物。瘤胃微生物组为发现新型微生物酶和代谢物(包括AMP)提供了一种未充分开发的资源。使用功能筛选和计算方法,我们确定了181个潜在的新的抗菌肽从瘤胃细菌宏基因组。在这里,我们表明,三个选定的抗菌肽(Lynronne-1,Lynronne-2和Lynronne-3)是有效的对许多细菌病原体,包括耐甲氧西林金黄色葡萄球菌(MRSA)。亚致死暴露于这些AMP 25天后,未观察到MRSA敏感性降低。抗菌肽优先结合细菌膜脂,并诱导膜通透性,导致细胞质渗漏。局部施用Lynronne-1(10%w/v)至MRSA伤口感染的小鼠模型引起细菌计数的显著减少,这与用2%莫匹罗星软膏的治疗相当。我们的研究结果表明,瘤胃微生物组可能为未来的治疗应用提供可行的替代抗菌剂。
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-resistantStaphylococcus 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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