Multifunctional nutrient-binding proteins adapt human symbiotic bacteria for glycan competition in the gut by separately promoting enhanced sensing and catalysis.
Multifunctional nutrient-binding proteins adapt human symbiotic bacteria for glycan competition in the gut by separately promoting enhanced sensing and catalysis.
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DOI：
10.1128/mbio.01441-14
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发表时间：
2014-09-09
期刊：
影响因子：
6.4
通讯作者：
Martens EC
中科院分区：
文献类型：
--
作者：
Cameron EA;Kwiatkowski KJ;Lee BH;Hamaker BR;Koropatkin NM;Martens EC
为了争夺流入其生态系统的营养物质的动态流，结肠细菌必须对新资源迅速作出反应，然后一旦发现它们就有效地分解代谢它们。多形拟杆菌淀粉利用系统（Bacteroides thetaiotaomicron starch utilization system，Sus）是肠道共生菌获取营养的模型，它包含数千个相关的Sus样系统。四个猪外膜蛋白（SusD，-E，-F，和-G）的结构研究表明，它们含有共8个淀粉结合位点，我们证明，使用遗传和生化方法，在体外和体内的gnotobiotic小鼠的淀粉代谢中发挥不同的作用。SusD的同源物在人类微生物组中丰富，对于可用淀粉的初始感测至关重要，允许在比没有此功能低得多的浓度下进行sus转录激活。相比之下，横跨SusE、-F和-G的七个额外结合位点对于sus激活是不必要的。然而，它们以依赖于细菌多糖胶囊表达的方式优化淀粉上的生长速率，这表明它们已经进化到抵消由这种结构产生的扩散屏障。这些发现证明了具有相似生化行为的蛋白质如何在细胞适应营养素的不同阶段发挥正交功能。最后，我们证明了在gnotobiotic小鼠喂食富含淀粉的饮食，Sus结合位点赋予竞争优势，B。多形微生物以依赖于其它定殖微生物的方式在体内存在。这项研究揭示了人类微生物组中碳水化合物结合蛋白的数量优势家族如何实现单独的，有时是合作的作用，以优化肠道细菌的营养获取。我们的肠道里有数万亿的共生微生物。这种微生物群落贡献的一个关键功能是降解我们饮食中大部分复杂碳水化合物的能力，这些碳水化合物不仅在每餐之间变化，而且不能被我们自己的身体消化。一组数量丰富的肠道细菌称为拟杆菌，在人类和其他动物的碳水化合物消化中起着重要作用。目前，允许这种细菌群快速响应可用碳水化合物并随后有效消化它们的机制尚不清楚。在这里，我们提出了四个碳水化合物结合蛋白存在于拟杆菌的一个成员的新功能，揭示了这些蛋白质在初始营养传感或随后的消化中发挥独特的和可分离的作用。由于所研究的蛋白质家族在几乎所有人类和动物的其他肠道细菌中都有很多，因此我们的研究结果对于了解共生微生物如何帮助人类消化至关重要。
To compete for the dynamic stream of nutrients flowing into their ecosystem, colonic bacteria must respond rapidly to new resources and then catabolize them efficiently once they are detected. The Bacteroides thetaiotaomicron starch utilization system (Sus) is a model for nutrient acquisition by symbiotic gut bacteria, which harbor thousands of related Sus-like systems. Structural investigation of the four Sus outer membrane proteins (SusD, -E, -F, and -G) revealed that they contain a total of eight starch-binding sites that we demonstrated, using genetic and biochemical approaches, to play distinct roles in starch metabolism in vitro and in vivo in gnotobiotic mice. SusD, whose homologs are abundant in the human microbiome, is critical for the initial sensing of available starch, allowing sus transcriptional activation at much lower concentrations than without this function. In contrast, seven additional binding sites across SusE, -F, and -G are dispensable for sus activation. However, they optimize the rate of growth on starch in a manner dependent on the expression of the bacterial polysaccharide capsule, suggesting that they have evolved to offset the diffusion barrier created by this structure. These findings demonstrate how proteins with similar biochemical behavior can serve orthogonal functions during different stages of cellular adaptation to nutrients. Finally, we demonstrated in gnotobiotic mice fed a starch-rich diet that the Sus binding sites confer a competitive advantage to B. thetaiotaomicron in vivo in a manner that is dependent on other colonizing microbes. This study reveals how numerically dominant families of carbohydrate-binding proteins in the human microbiome fulfill separate and sometimes cooperative roles to optimize gut commensal bacteria for nutrient acquisition. Our intestinal tract harbors trillions of symbiotic microbes. A critical function contributed by this microbial community is the ability to degrade most of the complex carbohydrates in our diet, which not only change from meal to meal but also cannot be digested by our own bodies. A numerically abundant group of gut bacteria called the Bacteroidetes plays a prominent role in carbohydrate digestion in humans and other animals. Currently, the mechanisms that allow this bacterial group to rapidly respond to available carbohydrates and then digest them efficiently are unclear. Here, we present novel functions for four carbohydrate-binding proteins present in one member of the Bacteroidetes, revealing that these proteins serve unique and separable roles in either initial nutrient sensing or subsequent digestion. Because the protein families investigated are numerous in other gut bacteria colonizing nearly all humans and animals, our findings are fundamentally important to understanding how symbiotic microbes assist human digestion.