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A hybrid two-component system protein of a prominent human gut symbiont couples glycan sensing in vivo to carbohydrate metabolism
Erica D. Sonnenburg,
Justin L. Sonnenburg,
Jill K. Manchester,
Elizabeth E. Hansen,
Herbert C. Chiang, and
Jeffrey I. Gordon*
Center for Genome Sciences, Washington University School of Medicine, St. Louis, MO 63108
Contributed by Jeffrey I. Gordon, April 21, 2006
Abstract:Bacteroides thetaiotaomicron is a prominent member of our normaladult intestinal microbial community and a useful model forstudying the foundations of humanbacterial mutualismin our densely populated distal gut microbiota. A central questionis how members of this microbiota sense nutrients and implementan appropriate metabolic response. B. thetaiotaomicron containsa large number of glycoside hydrolases not represented in ourown proteome, plus a markedly expanded collection of hybridtwo-component system (HTCS) proteins that incorporate all domainsfound in classical two-component environmental sensors intoone polypeptide. To understand the role of HTCS in nutrientsensing, we used B. thetaiotaomicron GeneChips to characterizetheir expression in gnotobiotic mice consuming polysaccharide-richor -deficient diets. One HTCS, BT3172, was selected for furtheranalysis because it is induced in vivo by polysaccharides, andits absence reduces B. thetaiotaomicron fitness in polysaccharide-richdiet-fed mice. Functional genomic and biochemical analyses ofWT and BT3172-deficient strains in vivo and in vitro disclosedthat -mannosides induce BT3172 expression, which in turn inducesexpression of secreted -mannosidases. Yeast two-hybrid screensrevealed that the cytoplasmic portion of BT3172's sensor domainserves as a scaffold for recruiting glucose-6-phosphate isomeraseand dehydrogenase. These interactions are a unique feature ofBT3172 and specific for the cytoplasmic face of its sensor domain.Loss of BT3172 reduces glycolytic pathway activity in vitroand in vivo. Thus, this HTCS functions as a metabolic reactioncenter, coupling nutrient sensing to dynamic regulation of monosaccharidemetabolism. An expanded repertoire of HTCS proteins with diversifiedsensor domains may be one reason for B. thetaiotaomicron's successin our intestinal ecosystem.
Key Words:Bacteroides thetaiotaomicron glycoside hydrolases gut microbial ecology metabolic regulation signal transduction
Freely available online through the PNAS open access option.
Author contributions: E.D.S. and J.I.G. designed research; E.D.S.,J.L.S., J.K.M., E.E.H., and H.C.C. performed research; E.D.S.and H.C.C. contributed new reagents/analytic tools; E.D.S.,J.L.S., J.K.M., E.E.H., and J.I.G. analyzed data; and E.D.S.and J.I.G. wrote the paper.
Conflict of interest statement: No conflicts declared.