Marine Mammal Microbiota Yields Novel Antibiotic with Potent Activity Against Clostridium difficile,ACS Infectious Diseases

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Marine Mammal Microbiota Yields Novel Antibiotic with Potent Activity Against Clostridium difficile
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2017-10-18 00:00:00 , DOI: 10.1021/acsinfecdis.7b00105
Jessica L. Ochoa ₁ , Laura M. Sanchez _{1,

2} , Byoung-Mo Koo ₃ , Jennifer S. Doherty ₃ , Manohary Rajendram ₄ , Kerwyn Casey Huang _{4,

5} , Carol A. Gross ₃ , Roger G. Linington _{1,

6}

Affiliation

The recent explosion of research on the microbiota has highlighted the important interplay between commensal microorganisms and the health of their cognate hosts. Metabolites isolated from commensal bacteria have been demonstrated to possess a range of antimicrobial activities, and it is widely believed that some of these metabolites modulate host behavior, affecting predisposition to disease and pathogen invasion. Our access to the local marine mammal stranding network and previous successes in mining the fish microbiota poised us to test the hypothesis that the marine mammal microbiota is a novel source of commensal bacteria-produced bioactive metabolites. Examination of intestinal contents from five marine mammals led to the identification of a Micromonospora strain with potent and selective activity against a panel of Gram-positive pathogens and no discernible human cytotoxicity. Compound isolation afforded a new complex glycosylated polyketide, phocoenamicin, with potent activity against the intestinal pathogen Clostridium difficile, an organism challenging to treat in hospital settings. Use of our activity-profiling platform, BioMAP, clustered this metabolite with other known ionophore antibiotics. Fluorescence imaging and flow cytometry confirmed that phocoenamicin is capable of shifting membrane potential without damaging membrane integrity. Thus, exploration of gut microbiota in hosts from diverse environments can serve as a powerful strategy for the discovery of novel antibiotics against human pathogens.

中文翻译：

海洋哺乳动物菌群产生具有抗艰难梭菌活性的新型抗生素。

最近有关微生物群的研究激增，突显了共生微生物与其相关宿主健康之间的重要相互作用。已证明，从共生细菌中分离的代谢物具有一系列抗菌活性，并且人们普遍认为，其中一些代谢物会调节宿主的行为，从而影响疾病和病原体入侵的易感性。我们对当地海洋哺乳动物搁浅网络的访问以及先前在鱼类微生物群中的成功开采，使我们检验了以下假设，即海洋哺乳动物微生物群是共生细菌产生的生物活性代谢产物的新来源。对五种海洋哺乳动物肠道内容物的检查导致发现了微型单孢菌菌株对一组革兰氏阳性病原体具有有效和选择性的活性，并且没有明显的人类细胞毒性。化合物的分离提供了一种新的复杂的糖基化聚酮化合物phoenenamicin，具有有效抵抗肠道病原体艰难梭状芽胞杆菌（Clostridium difficile）的活性，艰难梭菌是在医院环境中难以治疗的生物。使用我们的活性分析平台BioMAP，可以将这种代谢物与其他已知的离子载体抗生素聚集在一起。荧光成像和流式细胞仪证实，凤凰霉素能够转移膜电位而不会损害膜的完整性。因此，在来自不同环境的宿主中探索肠道菌群可以作为发现针对人类病原体的新型抗生素的有力策略。

更新日期：2017-10-18

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