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特定的生态进化环境在小鼠肠道中揭示了大肠杆菌的代谢多样性。

Specific Eco-evolutionary Contexts in the Mouse Gut Reveal Escherichia coli Metabolic Versatility.

机构信息

Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal.

Instituto Gulbenkian de Ciência, 2780-156 Oeiras, Portugal; Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, 2780-157 Oeiras, Portugal.

出版信息

Curr Biol. 2020 Mar 23;30(6):1049-1062.e7. doi: 10.1016/j.cub.2020.01.050. Epub 2020 Mar 5.

DOI:10.1016/j.cub.2020.01.050
PMID:32142697
Abstract

Members of the gut microbiota are thought to experience strong competition for nutrients. However, how such competition shapes their evolutionary dynamics and depends on intra- and interspecies interactions is poorly understood. Here, we test the hypothesis that Escherichia coli evolution in the mouse gut is more predictable across hosts in the absence of interspecies competition than in the presence of other microbial species. In support, we observed that lrp, a gene encoding a global regulator of amino acid metabolism, was repeatedly selected in germ-free mice 2 weeks after mono-colonization by this bacterium. We established that this specific genetic adaptation increased E. coli's ability to compete for amino acids, and analysis of gut metabolites identified serine and threonine as the metabolites preferentially consumed by E. coli in the mono-colonized mouse gut. Preference for serine consumption was further supported by testing a set of mutants that showed loss of advantage of an lrp mutant impaired in serine metabolism in vitro and in vivo. Remarkably, the presence of a single additional member of the microbiota, Blautia coccoides, was sufficient to alter the gut metabolome and, consequently, the evolutionary path of E. coli. In this environment, the fitness advantage of the lrp mutant bacteria is lost, and mutations in genes involved in anaerobic respiration were selected instead, recapitulating the eco-evolutionary context from mice with a complex microbiota. Together, these results highlight the metabolic plasticity and evolutionary versatility of E. coli, tailored to the specific ecology it experiences in the gut.

摘要

肠道微生物群的成员被认为会经历强烈的营养竞争。然而,这种竞争如何塑造它们的进化动态,以及它取决于种内和种间相互作用,这一点我们知之甚少。在这里,我们检验了这样一个假设,即在没有种间竞争的情况下,大肠杆菌在老鼠肠道中的进化比在存在其他微生物物种的情况下更具可预测性。支持这一假设的是,我们观察到,lrp 基因(编码氨基酸代谢全局调节剂的基因)在这种细菌单定植后 2 周的无菌小鼠中被反复选择。我们确定,这种特定的遗传适应性提高了大肠杆菌对氨基酸的竞争能力,对肠道代谢物的分析确定丝氨酸和苏氨酸是大肠杆菌在单定植小鼠肠道中优先消耗的代谢物。通过测试一组突变体进一步证实了对丝氨酸消耗的偏好,这些突变体在体外和体内都显示出在丝氨酸代谢中受损的 lrp 突变体的优势丧失。值得注意的是,单个额外的微生物成员——布劳氏菌 coccoides 的存在足以改变肠道代谢组,从而改变大肠杆菌的进化路径。在这种环境下,lrp 突变体细菌的适应优势丧失,而参与厌氧呼吸的基因的突变被选择,从而再现了具有复杂微生物组的小鼠的生态进化背景。总之,这些结果强调了大肠杆菌的代谢可塑性和进化多功能性,使其适应在肠道中经历的特定生态。

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