Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont.
Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont.
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DOI：
10.1074/jbc.m109.008094
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发表时间：
2009-07-03
期刊：
影响因子：
--
通讯作者：
Gordon JI
中科院分区：
文献类型：
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作者：
Martens EC;Roth R;Heuser JE;Gordon JI
人类远端肠道中的细菌已经进化出多种代谢复杂聚糖的能力，包括降解这些化合物作为营养物质的能力，以及将它们的组成糖组装成新的聚合物（如细胞外胶囊）的能力。人类肠道细菌拟杆菌（Bacteroides thetaiotaomicron）具有代谢宿主和饮食来源的聚糖的能力。它的基因组包含88个不同的多糖利用位点（PULs），用于复杂的多糖分解代谢和8个不同的荚膜多糖生物合成基因簇。在这里，我们研究了这种肠道共生体调节许多参与宿主粘蛋白o聚糖降解的PULs的主要机制之一；即，通过细胞包膜定位的tonb依赖性转运蛋白、胞质外功能σ因子和抗σ因子的协同相互作用进行转录调控，它们共同参与被称为反包膜信号传导的调控途径。出乎意料的是，我们发现几种不同的跨包膜信号开关参与了pull介导的o聚糖降解，也调节了荚膜多糖的合成。一种新的调控途径，依赖于o -聚糖靶向外膜蛋白的表达，控制着这种糖分解代谢和胶囊合成的协调调节。后一项发现为肠道定植过程中发生的复杂聚糖代谢、微生物生理学和宿主反应之间的动态相互作用提供了新的联系。
Bacteria in the distal human gut have evolved diverse abilities to metabolize complex glycans, including the capacity to degrade these compounds as nutrients and to assemble their component sugars into new polymers such as extracellular capsules. The human gut bacterium Bacteroides thetaiotaomicron is well endowed with the ability to metabolize both host- and diet-derived glycans. Its genome contains 88 different polysaccharide utilization loci (PULs) for complex glycan catabolism and eight different gene clusters for capsular polysaccharide biosynthesis. Here, we investigate one of the prominent mechanisms by which this gut symbiont regulates many PULs involved in host mucin O-glycan degradation; namely, transcriptional regulation via the concerted interactions of cell-envelope-localized TonB-dependent transporters, extra-cytoplasmic function σ factors and anti-σ factors, which participate together in a regulatory pathway termed trans-envelope signaling. Unexpectedly, we found that several different trans-envelope signaling switches involved in PUL-mediated O-glycan degradation also modulate capsular polysaccharide synthesis. A novel regulatory pathway, which is dependent on expression of O-glycan-targeting outer membrane proteins, governs this coordinated regulation of glycan catabolism and capsule synthesis. This latter finding provides a new link in the dynamic interplay between complex glycan metabolism, microbial physiology, and host responses that occurs during colonization of the gut.