A Master Regulator of Bacteroides thetaiotaomicron Gut Colonization Controls Carbohydrate Utilization and an Alternative Protein Synthesis Factor.
A Master Regulator of Bacteroides thetaiotaomicron Gut Colonization Controls Carbohydrate Utilization and an Alternative Protein Synthesis Factor.
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多形拟杆菌肠道定植的主要调节因子控制碳水化合物的利用和替代蛋白质合成因子。
DOI：
10.1128/mbio.03221-19
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发表时间：
2020
期刊：
影响因子：
6.4
通讯作者：
Groisman,EduardoA
中科院分区：
文献类型：
--
作者：
Townsend2nd,GuyE;Han,Weiwei;Schwalm3rd,NathanD;Hong,Xinyu;Bencivenga-Barry,NatashaA;Goodman,AndrewL;Groisman,EduardoA
哺乳动物肠道的微生物定殖主要归因于利用该环境中可用的营养物质的能力。为了了解有益微生物如何与宿主建立关系，确定哪些其他能力促进肠道定植至关重要。我们现在报告说，有益微生物多形拟杆菌在小鼠肠道的定植需要肠道定植和碳水化合物利用的主要转录调节因子激活一个假定的翻译因子。为了确定这种名为BT4338的调节剂如何促进肠道定植，我们鉴定了BT4338调节的基因和BT4338结合的DNA序列。出乎意料的是，在BT4338失活时表达减少最多的基因是fusA 2，它指定了一个假定的翻译因子。我们确定BT4338激活的fusA 2在另一种拟杆菌中是保守的，并且是B中肠道定殖所必需的。因为在fusA 2启动子中缺少BT4338结合位点的突变体表现出与缺少fusA 2基因的突变体相似的定殖缺陷。此外，我们证明了BT4338促进肠道定植独立于其在碳水化合物利用中的作用，因为fusA 2基因是依赖于BT4338的碳水化合物利用的。我们的研究结果表明，微生物肠道定植需要使用替代的蛋白质合成因子。重要信息占据哺乳动物肠道的细菌已经进化出独特的策略，以在其环境中茁壮成长。拟杆菌生物体通常占人类肠道微生物的25 - 50%，从结构多样的复杂多糖（通常称为膳食纤维）中获得营养素。这种能力需要一个广泛的遗传库，协调调节，以实现那些专门利用环境中存在的膳食纤维的基因的表达。在这里，我们确定了膳食纤维利用和肠道定植所必需的转录调节因子的全局调节子。我们证明，这种转录因子调节数百个参与膳食纤维利用的基因，以及一个假定的翻译因子，用于在这些营养素上生长，但在肠道中生存所必需的。这些发现表明，肠道细菌通过专门的翻译因子协调细胞代谢和蛋白质合成，以促进哺乳动物肠道中的存活。
Microbial colonization of the mammalian gut is largely ascribed to the ability to utilize nutrients available in that environment. To understand how beneficial microbes establish a relationship with their hosts, it is crucial to determine what other abilities promote gut colonization. We now report that colonization of the murine gut by the beneficial microbe Bacteroides thetaiotaomicron requires activation of a putative translation factor by the major transcriptional regulator of gut colonization and carbohydrate utilization. To ascertain how this regulator—called BT4338—promotes gut colonization, we identified BT4338-regulated genes and BT4338-bound DNA sequences. Unexpectedly, the gene whose expression was most reduced uponBT4338inactivation wasfusA2, specifying a putative translation factor. We determined thatfusA2activation by BT4338 is conserved in anotherBacteroidesspecies and essential for gut colonization in B. thetaiotaomicron because a mutant lacking the BT4338 binding site in thefusA2promoter exhibited a colonization defect similar to that of a mutant lacking thefusA2gene. Furthermore, we demonstrated that BT4338 promotes gut colonization independently of its role in carbohydrate utilization because thefusA2gene was dispensable for utilization of carbohydrates that depend onBT4338. Our findings suggest that microbial gut colonization requires the use of alternative protein synthesis factors.IMPORTANCEThe bacteria occupying the mammalian gut have evolved unique strategies to thrive in their environment.Bacteroidesorganisms, which often comprise 25 to 50% of the human gut microbiota, derive nutrients from structurally diverse complex polysaccharides, commonly called dietary fibers. This ability requires an expansive genetic repertoire that is coordinately regulated to achieve expression of those genes dedicated to utilizing only those dietary fibers present in the environment. Here we identify the global regulon of a transcriptional regulator necessary for dietary fiber utilization and gut colonization. We demonstrate that this transcription factor regulates hundreds of genes putatively involved in dietary fiber utilization as well as a putative translation factor dispensable for growth on such nutrients but necessary for survival in the gut. These findings suggest that gut bacteria coordinate cellular metabolism with protein synthesis via specialized translation factors to promote survival in the mammalian gut.