Human Milk Oligosaccharide Utilization in Intestinal Bifidobacteria Is Governed by Global Transcriptional Regulator NagR.
Human Milk Oligosaccharide Utilization in Intestinal Bifidobacteria Is Governed by Global Transcriptional Regulator NagR.
复制标题
DOI：
10.1128/msystems.00343-22
复制
发表时间：
2022-10-26
期刊：
影响因子：
6.4
通讯作者：
中科院分区：
文献类型：
--
作者：
长双歧杆菌亚种乳杆菌是一种普遍存在的有益细菌，其定殖于人类新生儿肠道，并且独特地适于有效地利用人乳低聚糖（HMO）作为碳源和能源。多项研究集中于表征B中HMO利用机制的要素。长双歧杆菌婴儿亚种然而，这些分解代谢途径表达的调控机制仍然知之甚少。本研究中使用的生物信息学调节子重建方法涉及来自ROK家族的转录因子NagR作为编码B中的乳糖-N-二糖/半乳糖-N-二糖（LNB/GN B）、乳糖-N-四糖（LNT）和乳糖-N-新四糖（LNnT）利用途径的基因簇的负全局调节因子。长双歧杆菌婴儿亚种婴儿。这一猜想证实了转录组分析后，nagR基因失活和实验评估的结合重组NagR预测的DNA运营商。后一种方法还涉及N-乙酰葡糖胺（GlcNAc），LNT和LNnT催化剂的通用中间体，及其磷酸化衍生物作为合理的NagR转录效应子。在各种双歧杆菌谱系中的NagR调节子的重建揭示了多个潜在的调节子扩增事件，表明从祖先双歧杆菌中GlcNAc催化剂的局部调节子进化为控制B中含GlcNAc的宿主聚糖的混合物的利用的全局调节子。长双歧杆菌婴儿亚种双歧杆菌和两歧双歧杆菌。母乳喂养婴儿肠道中双歧杆菌的优势归因于这些细菌代谢母乳低聚糖（HMO）的能力。因此，个别的HMO如乳糖-N-四糖（LNT）和乳糖-N-新四糖（LNnT）被认为是有前途的益生元，可以刺激益生菌的生长，并为患有肠道微生物群发育受损（发育迟缓）的早产儿和营养不良儿童提供多种健康益处。然而，基于HMO的益生元的合理选择受到了目标益生菌中HMO利用的调控机制的不完全知识的阻碍。本研究描述了NagR介导的LNT和LNnT利用的转录调控在长双歧杆菌亚种。一群人。阐明的监管网络似乎最适合同时使用多种HMO，为在婴儿配方奶粉中添加HMO混合物（而不是单个成分）提供了理论依据。该研究还提供了对控制双歧杆菌中碳水化合物代谢的复杂调控网络的进化轨迹的见解。
Bifidobacterium longum subsp. infantis is a prevalent beneficial bacterium that colonizes the human neonatal gut and is uniquely adapted to efficiently use human milk oligosaccharides (HMOs) as a carbon and energy source. Multiple studies have focused on characterizing the elements of HMO utilization machinery in B. longum subsp. infantis; however, the regulatory mechanisms governing the expression of these catabolic pathways remain poorly understood. A bioinformatic regulon reconstruction approach used in this study implicated NagR, a transcription factor from the ROK family, as a negative global regulator of gene clusters encoding lacto-N-biose/galacto-N-biose (LNB/GNB), lacto-N-tetraose (LNT), and lacto-N-neotetraose (LNnT) utilization pathways in B. longum subsp. infantis. This conjecture was corroborated by transcriptome profiling upon nagR genetic inactivation and experimental assessment of binding of recombinant NagR to predicted DNA operators. The latter approach also implicated N-acetylglucosamine (GlcNAc), a universal intermediate of LNT and LNnT catabolism, and its phosphorylated derivatives as plausible NagR transcriptional effectors. Reconstruction of NagR regulons in various Bifidobacterium lineages revealed multiple potential regulon expansion events, suggesting evolution from a local regulator of GlcNAc catabolism in ancestral bifidobacteria to a global regulator controlling the utilization of mixtures of GlcNAc-containing host glycans in B. longum subsp. infantis and Bifidobacterium bifidum. IMPORTANCE The predominance of bifidobacteria in the gut of breastfed infants is attributed to the ability of these bacteria to metabolize human milk oligosaccharides (HMOs). Thus, individual HMOs such as lacto-N-tetraose (LNT) and lacto-N-neotetraose (LNnT) are considered promising prebiotics that would stimulate the growth of bifidobacteria and confer multiple health benefits to preterm and malnourished children suffering from impaired (stunted) gut microbiota development. However, the rational selection of HMO-based prebiotics is hampered by the incomplete knowledge of regulatory mechanisms governing HMO utilization in target bifidobacteria. This study describes NagR-mediated transcriptional regulation of LNT and LNnT utilization in Bifidobacterium longum subsp. infantis. The elucidated regulatory network appears optimally adapted to simultaneous utilization of multiple HMOs, providing a rationale to add HMO mixtures (rather than individual components) to infant formulas. The study also provides insights into the evolutionary trajectories of complex regulatory networks controlling carbohydrate metabolism in bifidobacteria.
登录
查看更多内容
影响因子：
12.2
作者：
Hirano R;Sakanaka M;Yoshimi K;Sugimoto N;Eguchi S;Yamauchi Y;Nara M;Maeda S;Ami Y;Gotoh A;Katayama T;Iida N;Kato T;Ohno H;Fukiya S;Yokota A;Nishimoto M;Kitaoka M;Nakai H;Kurihara S
通讯作者：
Kurihara S
影响因子：
4.6
作者：
Garrido D;Ruiz-Moyano S;Lemay DG;Sela DA;German JB;Mills DA
通讯作者：
Mills DA
影响因子：
6.4
作者：
Berger, Bernard;Porta, Nadine;Sprenger, Norbert
通讯作者：
Sprenger, Norbert
影响因子：
6
作者：
Alessandri G;van Sinderen D;Ventura M
通讯作者：
Ventura M
影响因子：
7
作者：
Garrido, Daniel;Nwosu, Charles;Mills, David A.
通讯作者：
Mills, David A.