The antimicrobial potential of Streptomyces from insect microbiomes
The antimicrobial potential of Streptomyces from insect microbiomes
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DOI：
10.1038/s41467-019-08438-0
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发表时间：
2019-01-31
影响因子：
16.6
通讯作者：
Currie, Cameron R.
中科院分区：
文献类型：
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作者：
Chevrette, Marc G.;Carlson, Caitlin M.;Currie, Cameron R.
抗菌素耐药性是一个全球性的健康危机，近几十年来几乎没有发现新的抗菌剂。天然产物，特别是来自链霉菌的天然产物，是大多数抗菌剂的来源，然而，专注于从土壤中发现链霉菌的活动在很大程度上重新发现了已知的化合物。对研究不足和共生源的调查取得了一些成功，但还没有研究系统地探索抗菌剂的微生物群。在这里，我们通过大规模分离、生物活性分析、基因组学、代谢组学和体内感染模型来评估来自昆虫微生物群的链霉菌作为新抗菌剂来源的独特进化谱系。昆虫相关的链霉菌比土壤链霉菌更能抑制抗药性病原体。基因组学和代谢组学揭示了它们不同的生物合成能力。此外，我们描述了环霉素，一种有效对抗多重耐药真菌病原体的新分子。来自昆虫微生物组的链霉菌的进化轨迹影响了它们的生物合成潜力和抑制耐药病原体的能力，支持了这一来源在加强未来抗菌药物发现方面的前景。
Antimicrobial resistance is a global health crisis and few novel antimicrobials have been discovered in recent decades. Natural products, particularly from Streptomyces, are the source of most antimicrobials, yet discovery campaigns focusing on Streptomyces from the soil largely rediscover known compounds. Investigation of understudied and symbiotic sources has seen some success, yet no studies have systematically explored microbiomes for antimicrobials. Here we assess the distinct evolutionary lineages of Streptomyces from insect microbiomes as a source of new antimicrobials through large-scale isolations, bioactivity assays, genomics, metabolomics, and in vivo infection models. Insect-associated Streptomyces inhibit antimicrobial-resistant pathogens more than soil Streptomyces. Genomics and metabolomics reveal their diverse biosynthetic capabilities. Further, we describe cyphomycin, a new molecule active against multidrug resistant fungal pathogens. The evolutionary trajectories of Streptomyces from the insect microbiome influence their biosynthetic potential and ability to inhibit resistant pathogens, supporting the promise of this source in augmenting future antimicrobial discovery.