A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism

Abstract

Bacteroides thetaiotaomicron is a prominent member of our normal adult intestinal microbial community and a useful model for studying the foundations of human-bacterial mutualism in our densely populated distal gut microbiota. A central question is how members of this microbiota sense nutrients and implement an appropriate metabolic response. B. thetaiotaomicron contains a large number of glycoside hydrolases not represented in our own proteome, plus a markedly expanded collection of hybrid twocomponent system (HTCS) proteins that incorporate all domains found in classical two-component environmental sensors into one polypeptide. To understand the role of HTCS in nutrient sensing, we used B. thetaiotaomicron GeneChips to characterize their expression in gnotobiotic mice consuming polysaccharide-rich or -deficient diets. One HTCS, BT3172, was selected for further analysis because it is induced in vivo by polysaccharides, and its absence reduces B. thetaiotaomicron fitness in polysaccharide-rich diet-fed mice. Functional genomic and biochemical analyses of WT and BT3172-deficient strains in vivo and in vitro disclosed that ␣-mannosides induce BT3172 expression, which in turn induces expression of secreted ␣-mannosidases. Yeast two-hybrid screens revealed that the cytoplasmic portion of BT3172's sensor domain serves as a scaffold for recruiting glucose-6-phosphate isomerase and dehydrogenase. These interactions are a unique feature of BT3172 and specific for the cytoplasmic face of its sensor domain. Loss of BT3172 reduces glycolytic pathway activity in vitro and in vivo. Thus, this HTCS functions as a metabolic reaction center, coupling nutrient sensing to dynamic regulation of monosaccharide metabolism. An expanded repertoire of HTCS proteins with diversified sensor domains may be one reason for B. thetaiotaomicron's success in our intestinal ecosystem.Bacteroides thetaiotaomicron ͉ glycoside hydrolases ͉ gut microbial ecology ͉ metabolic regulation ͉ signal transduction

Bacteroides: the Good, the Bad, and the Nitty-Gritty

“…Typically, expression of one of the capsular polysaccharide synthesis loci (cps3) is upregulated when polysaccharides are scarce. In a mutant deficient in BT3172, expression of cps3 is increased even in the presence of a medium rich in polysaccharides, suggesting that BT3172 is important for the bacterium to properly interpret its nutrient landscape in terms of adequate supply of polysaccharides (263).…”

“…In one system, nutrient sensing is coupled to regulation of monosaccharide metabolism (263). BT3172 belongs to this family of proteins, and its expression is regulated by polysaccharides in the environment.…”

Markov random fields reveal an N-terminal double beta-propeller motif as part of a bacterial hybrid two-component sensor system

“…Frequently, such processes are mediated by two-component sensor proteins, involving a usually membrane-bound sensor protein, and a response regulator. A set of 32 unusual hybrid periplasmicsensing two-component sensor histidine kinases were discovered in the human gut symbiont Bacteroides thetaiotaomicron (2). These hybrid two-component sensor systems (HTCS) were unusual in that they incorporated all of the domains found in the classical two-component system into a single polypeptide (3).…”

“…These hybrid two-component sensor systems (HTCS) were unusual in that they incorporated all of the domains found in the classical two-component system into a single polypeptide (3). Sonnenburg et al (2) hypothesized that the HTCS proteins were involved in how these microbiota sense diverse nutrients and implement an appropriate metabolic response, and showed that loss of one of these HTCS proteins, BT3172, reduced glycotic pathway activity. They also found that the sensor domains of the HTCS proteins were less highly conserved than their intracellular signaling domains, suggesting that the HTCS proteins have diversified to respond to a variety of signals while conserving their means of intracellular signal transduction.…”

Sake and Beer Spoilage Lactic Acid Bacteria - A Review

“…For example, bifidobacteria have developed intricate mechanisms to inhabit the mucus layer of intestinal tracts of mammals, where many other microorganisms cannot persist 30,52,88,93,98,124 . It has been known that bifidobacteria have acquired the ability to adhere to the mucosal barrier system of the intestinal tract, while developing the resistance to bactericidal bile 35 .…”