Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum
Molecular Insight into Evolution of Symbiosis between Breast-Fed Infants and a Member of the Human Gut Microbiome Bifidobacterium longum
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DOI：
10.1016/j.chembiol.2017.03.012
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发表时间：
2017-04-20
影响因子：
8.6
通讯作者：
Fushinobu, Shinya
中科院分区：
文献类型：
--
作者：
Yamada, Chihaya;Gotoh, Aina;Fushinobu, Shinya
母乳喂养的婴儿通常具有丰富的双歧杆菌菌群，最近的研究表明，人乳寡糖（HMOs）选择性地促进双歧杆菌的生长。两歧双歧杆菌拥有糖苷水解酶家族20乳酸- n -生物苷酶，用于从乳汁中丰富的乳酸- n -四糖（乳汁中特有的HMO）中释放乳酸- n -二糖I。longum有一种非分类酶（LnbX）。在这里，我们确定了LnbX催化结构域的晶体结构，并为创建新的糖苷水解酶家族GH136提供了证据。该结构与抑制和突变研究相结合，为该酶的分子机制和更广泛的底物特异性提供了见解。此外，通过遗传学研究，我们发现lnbX是长芽孢杆菌在乳酸- n -四糖上生长所必需的，也是母乳喂养婴儿肠道中持续存在的关键遗传因素。总的来说，这项研究揭示了人类和双歧杆菌在婴儿肠道中共生的可能进化途径。
Breast-fed infants generally have a bifidobacteriarich microbiota with recent studies indicating that human milk oligosaccharides (HMOs) selectively promote bifidobacterial growth. Bifidobacterium bifidum possesses a glycoside hydrolase family 20 lacto-N-biosidase for liberating lacto-N-biose I from lacto-N-tetraose, an abundant HMO unique to human milk, while Bifidobacterium longum subsp. longum has a non-classified enzyme (LnbX). Here, we determined the crystal structure of the catalytic domain of LnbX and provide evidence for creation of a novel glycoside hydrolase family, GH136. The structure, in combination with inhibition and mutation studies, provides insight into the molecular mechanism and broader substrate specificity of this enzyme. Moreover, through genetic studies, we show that lnbX is indispensable for B. longum growth on lacto-N-tetraose and is a key genetic factor for persistence in the gut of breast-fed infants. Overall, this study reveals possible evolutionary routes for the emergence of symbiosis between humans and bifidobacterial species in the infant gut.