Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis
Evolutionary adaptation in fucosyllactose uptake systems supports bifidobacteria-infant symbiosis
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DOI：
10.1126/sciadv.aaw7696
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发表时间：
2019-08-01
期刊：
影响因子：
13.6
通讯作者：
Katayama, Takane
中科院分区：
文献类型：
--
作者：
Sakanaka, Mikiyasu;Hansen, Morten Ejby;Katayama, Takane
在婴儿期建立的人类肠道微生物群对健康有持续的影响。体外研究表明，母乳中的人乳低聚糖（HMO）促进婴儿肠道中富含双歧杆菌的微生物群的形成;然而，潜在的分子机制仍然难以捉摸。在这里，我们的特点是两个功能不同，但重叠的岩藻糖基乳糖转运蛋白（FL转运蛋白-1和-2）从长双歧杆菌亚种E101。粪便DNA和HMO消耗分析，结合沉积的宏基因组数据挖掘，揭示了FL转运蛋白-2主要与母乳喂养的婴儿肠道中富含细菌的微生物群形成相关。FL转运蛋白-2与2 '-岩藻糖基乳糖和3-岩藻糖基乳糖复合的溶质结合蛋白（SBP）的结构分析，以及两种FL转运蛋白的SBP同源物的系统发育分析，突出了双歧杆菌对HMO的独特适应策略，其中功能获得性突变使FL转运蛋白-2能够有效捕获主要的岩藻糖基化HMO。我们的研究结果提供了一个分子洞察HMO介导的共生和共生细菌和人类之间的共同进化。
The human gut microbiota established during infancy has persistent effects on health. In vitro studies have suggested that human milk oligosaccharides (HMOs) in breast milk promote the formation of a bifidobacteria-rich microbiota in infant guts; however, the underlying molecular mechanism remains elusive. Here, we characterized two functionally distinct but overlapping fucosyllactose transporters (FL transporter-1 and -2) from Bifidobacterium longum subspecies infantis. Fecal DNA and HMO consumption analyses, combined with deposited metagenome data mining, revealed that FL transporter-2 is primarily associated with the bifidobacteria-rich microbiota formation in breast-fed infant guts. Structural analyses of the solute-binding protein (SBP) of FL transporter-2 complexed with 2'-fucosyllactose and 3-fucosyllactose, together with phylogenetic analysis of SBP homologs of both FL transporters, highlight a unique adaptation strategy of Bifidobacterium to HMOs, in which the gain-of-function mutations enable FL transporter-2 to efficiently capture major fucosylated HMOs. Our results provide a molecular insight into HMO-mediated symbiosis and coevolution between bifidobacteria and humans.