The rumen microbiome: an underexplored resource for novel antimicrobial discovery.
The rumen microbiome: an underexplored resource for novel antimicrobial discovery.
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DOI：
10.1038/s41522-017-0042-1
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发表时间：
2017
影响因子：
9.2
通讯作者：
Huws SA
中科院分区：
文献类型：
--
作者：
Oyama LB;Girdwood SE;Cookson AR;Fernandez-Fuentes N;Privé F;Vallin HE;Wilkinson TJ;Golyshin PN;Golyshina OV;Mikut R;Hilpert K;Richards J;Wootton M;Edwards JE;Maresca M;Perrier J;Lundy FT;Luo Y;Zhou M;Hess M;Mantovani HC;Creevey CJ;Huws SA
抗菌肽（AMP）是针对多重耐药细菌的有前途的候选药物。瘤胃微生物组为发现新型微生物酶和代谢物（包括 AMP）提供了尚未开发的资源。使用功能筛选和计算方法，我们从瘤胃细菌宏基因组中鉴定出 181 种潜在的新型 AMP。在这里，我们证明了选定的三种 AMP（Lynronne-1、Lynronne-2 和 Lynronne-3）可有效对抗多种细菌病原体，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 敏感性下降。 AMP 优先与细菌膜脂结合并诱导膜通透性，导致细胞质渗漏。对 MRSA 伤口感染小鼠模型局部施用 Lynronne-1（10% w/v）可引起细菌计数显着减少，与 2% 莫匹罗星软膏治疗相当。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药物。反刍动物肠道微生物产生的抗微生物分子可能成为对抗抗生素耐药性感染的新武器。由英国贝尔法斯特女王大学 Sharon Huws 领导的国际研究小组在牛、绵羊和山羊等动物的瘤胃中发现了三种抗菌肽。这些肽（短蛋白）在针对几种临床上重要的耐药感染的实验室试验中表现出高度活性。其中包括耐甲氧西林金黄色葡萄球菌（MRSA），这是一种臭名昭著的导致危及生命的感染的原因，特别是对于免疫力较弱的患者。人们对使用肽作为现有抗生素的替代品越来越感兴趣。通过检查分子数据“库”而得出的研究结果表明，瘤胃是一种尚未开发的资源，可能含有许多医学上有用的抗菌素。应进一步研究可能性，并在临床条件下测试有前途的分子。
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. Anti-microbial molecules made by microbes in the gut of ruminant animals could become new weapons against antibiotic-resistant infections. An international team of researchers led by Sharon Huws at Queen’s University Belfast, UK, identified three anti-microbial peptides in the rumen of animals such as cattle, sheep and goats. The peptides—short proteins—were highly active in laboratory trials against several clinically important drug-resistant infections. These included methicillin resistant Staphylococcus aureus (MRSA), a notorious cause of life-threatening infections, especially in patients with weakened immunity. There is growing interest in using peptides as alternatives to existing antibiotics. The findings, initiated by examining a ‘library’ of molecular data, suggest that the rumen is an under-explored resource that may harbor many medically useful antimicrobials. The possibilities should be investigated further, with promising molecules being tested in clinical conditions.
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影响因子：
4.2
作者：
Hu F;Wu Q;Song S;She R;Zhao Y;Yang Y;Zhang M;Du F;Soomro MH;Shi R
通讯作者：
Shi R
影响因子：
3.1
作者：
Alder, Jeffrey;Eisenstein, Barry
通讯作者：
Eisenstein, Barry
DOI：
10.1007/s00249-008-0352-6
发表时间：
2008-11-01
影响因子：
2
作者：
Dennison, Sarah R.;Kim, Young Soo;Phoenix, David A.
通讯作者：
Phoenix, David A.
影响因子：
--
作者：
Jorgensen, J. H.
通讯作者：
Jorgensen, J. H.
影响因子：
4.2
作者：
Hammami R;Zouhir A;Ben Hamida J;Fliss I
通讯作者：
Fliss I