Wexler Aaron G, Bao Yiqiao, Whitney John C, Bobay Louis-Marie, Xavier Joao B, Schofield Whitman B, Barry Natasha A, Russell Alistair B, Tran Bao Q, Goo Young Ah, Goodlett David R, Ochman Howard, Mougous Joseph D, Goodman Andrew L
Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT 06510; Microbial Sciences Institute, Yale University School of Medicine, West Haven, CT 06516;
Department of Microbiology, University of Washington School of Medicine, Seattle, WA 98195;
Proc Natl Acad Sci U S A. 2016 Mar 29;113(13):3639-44. doi: 10.1073/pnas.1525637113. Epub 2016 Mar 8.
The human gut microbiome is a dynamic and densely populated microbial community that can provide important benefits to its host. Cooperation and competition for nutrients among its constituents only partially explain community composition and interpersonal variation. Notably, certain human-associated Bacteroidetes--one of two major phyla in the gut--also encode machinery for contact-dependent interbacterial antagonism, but its impact within gut microbial communities remains unknown. Here we report that prominent human gut symbionts persist in the gut through continuous attack on their immediate neighbors. Our analysis of just one of the hundreds of species in these communities reveals 12 candidate antibacterial effector loci that can exist in 32 combinations. Through the use of secretome studies, in vitro bacterial interaction assays and multiple mouse models, we uncover strain-specific effector/immunity repertoires that can predict interbacterial interactions in vitro and in vivo, and find that some of these strains avoid contact-dependent killing by accumulating immunity genes to effectors that they do not encode. Effector transmission rates in live animals can exceed 1 billion events per minute per gram of colonic contents, and multiphylum communities of human gut commensals can partially protect sensitive strains from these attacks. Together, these results suggest that gut microbes can determine their interactions through direct contact. An understanding of the strategies human gut symbionts have evolved to target other members of this community may provide new approaches for microbiome manipulation.
人类肠道微生物群是一个动态且人口密集的微生物群落,能为其宿主带来重要益处。其组成部分之间对营养物质的合作与竞争只能部分解释群落组成和个体差异。值得注意的是,某些与人类相关的拟杆菌门(肠道中两个主要门类之一)也编码接触依赖性细菌间拮抗作用的机制,但其在肠道微生物群落中的影响仍不明确。在此,我们报告称,人类肠道中的主要共生菌通过持续攻击其直接邻居而在肠道中持续存在。我们对这些群落中数百个物种之一的分析揭示了12个候选抗菌效应基因座,它们可以以32种组合形式存在。通过蛋白质分泌组研究、体外细菌相互作用试验和多种小鼠模型,我们发现了菌株特异性的效应器/免疫库,这些库可以预测体外和体内的细菌间相互作用,并发现其中一些菌株通过积累针对它们不编码的效应器的免疫基因来避免接触依赖性杀伤。在活体动物中,效应器的传递速率可超过每克结肠内容物每分钟10亿次事件,并且人类肠道共生菌的多门类群落可以部分保护敏感菌株免受这些攻击。总之,这些结果表明肠道微生物可以通过直接接触来决定它们之间的相互作用。了解人类肠道共生菌进化出的针对该群落其他成员的策略,可能会为微生物组的调控提供新方法。