Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


Logo for

PNAS 103 (23): 8834-8839

Copyright © 2006 by the National Academy of Sciences.


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 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 two-component 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 {alpha}-mannosides induce BT3172 expression, which in turn induces expression of secreted {alpha}-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.

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.

Data deposition: The GeneChip data sets reported in this paper have been deposited in the Gene Expression Omnibus database, (accession nos. GSM40917GSM40926, GSM40886GSM40888, GSM40897GSM40899, GSM40902GSM40906, and GSE4703).

*To whom correspondence should be addressed. E-mail: jgordon{at}

© 2006 by The National Academy of Sciences of the USA

The Genome of the Alga-Associated Marine Flavobacterium Formosa agariphila KMM 3901T Reveals a Broad Potential for Degradation of Algal Polysaccharides.
A. J. Mann, R. L. Hahnke, S. Huang, J. Werner, P. Xing, T. Barbeyron, B. Huettel, K. Stuber, R. Reinhardt, J. Harder, et al. (2013)
Appl. Envir. Microbiol. 79, 6813-6822
   Abstract »    Full Text »    PDF »
Intramolecular arrangement of sensor and regulator overcomes relaxed specificity in hybrid two-component systems.
G. E. Townsend II, V. Raghavan, I. Zwir, and E. A. Groisman (2013)
PNAS 110, E161-E169
   Abstract »    Full Text »    PDF »
A multicomponent sugar phosphate sensor system specifically induced in Bacillus cereus during infection of the insect gut.
F. Song, Q. Peng, J. Brillard, C. Buisson, M. de Been, T. Abee, V. Broussolle, D. Huang, J. Zhang, D. Lereclus, et al. (2012)
FASEB J 26, 3336-3350
   Abstract »    Full Text »    PDF »
Sulfatases and a Radical S-Adenosyl-L-methionine (AdoMet) Enzyme Are Key for Mucosal Foraging and Fitness of the Prominent Human Gut Symbiont, Bacteroides thetaiotaomicron.
A. Benjdia, E. C. Martens, J. I. Gordon, and O. Berteau (2011)
J. Biol. Chem. 286, 25973-25982
   Abstract »    Full Text »    PDF »
Transcriptomic Analyses of Xylan Degradation by Prevotella bryantii and Insights into Energy Acquisition by Xylanolytic Bacteroidetes.
D. Dodd, Y.-H. Moon, K. Swaminathan, R. I. Mackie, and I. K. O. Cann (2010)
J. Biol. Chem. 285, 30261-30273
   Abstract »    Full Text »    PDF »
Markov random fields reveal an N-terminal double beta-propeller motif as part of a bacterial hybrid two-component sensor system.
M. Menke, B. Berger, and L. Cowen (2010)
PNAS 107, 4069-4074
   Abstract »    Full Text »    PDF »
Complex Glycan Catabolism by the Human Gut Microbiota: The Bacteroidetes Sus-like Paradigm.
E. C. Martens, N. M. Koropatkin, T. J. Smith, and J. I. Gordon (2009)
J. Biol. Chem. 284, 24673-24677
   Abstract »    Full Text »    PDF »
Effects of probiotics and commensals on intestinal epithelial physiology: implications for nutrient handling.
S. C. Resta (2009)
J. Physiol. 587, 4169-4174
   Abstract »    Full Text »    PDF »
Regulation of the Xylan-degrading Apparatus of Cellvibrio japonicus by a Novel Two-component System.
K. Emami, E. Topakas, T. Nagy, J. Henshaw, K. A. Jackson, K. E. Nelson, E. F. Mongodin, J. W. Murray, R. J. Lewis, and H. J. Gilbert (2009)
J. Biol. Chem. 284, 1086-1096
   Abstract »    Full Text »    PDF »
Genes and Molecules of Lactobacilli Supporting Probiotic Action.
S. Lebeer, J. Vanderleyden, and S. C. J. De Keersmaecker (2008)
Microbiol. Mol. Biol. Rev. 72, 728-764
   Abstract »    Full Text »    PDF »
Bacteroides: the Good, the Bad, and the Nitty-Gritty.
H. M. Wexler (2007)
Clin. Microbiol. Rev. 20, 593-621
   Abstract »    Full Text »    PDF »
Genomic and metabolic adaptations of Methanobrevibacter smithii to the human gut.
B. S. Samuel, E. E. Hansen, J. K. Manchester, P. M. Coutinho, B. Henrissat, R. Fulton, P. Latreille, K. Kim, R. K. Wilson, and J. I. Gordon (2007)
PNAS 104, 10643-10648
   Abstract »    Full Text »    PDF »
The Lysine Decarboxylase CadA Protects Escherichia coli Starved of Phosphate against Fermentation Acids.
P. L. Moreau (2007)
J. Bacteriol. 189, 2249-2261
   Abstract »    Full Text »    PDF »
Functional Genomic and Metabolic Studies of the Adaptations of a Prominent Adult Human Gut Symbiont, Bacteroides thetaiotaomicron, to the Suckling Period.
M. K. Bjursell, E. C. Martens, and J. I. Gordon (2006)
J. Biol. Chem. 281, 36269-36279
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882