title: Multiple Signals Govern Utilization of a Polysaccharide in the Gut Bacterium Bacteroides thetaiotaomicron.
abstract: The utilization of simple sugars is widespread across all domains of life. In contrast, the breakdown of complex carbohydrates is restricted to a subset of organisms. A regulatory paradigm for integration of complex polysaccharide breakdown with simple sugar utilization was established in the mammalian gut symbiont Bacteroides thetaiotaomicron, whereby sensing of monomeric fructose regulates catabolism of both fructose and polymeric fructans. We now report that a different regulatory paradigm governs utilization of monomeric arabinose and the arabinose polymer arabinan. We establish that (i) arabinan utilization genes are controlled by a transcriptional activator that responds to arabinan and by a transcriptional repressor that responds to arabinose, (ii) arabinose utilization genes are regulated directly by the arabinose-responding repressor but indirectly by the arabinan-responding activator, and (iii) activation of both arabinan and arabinose utilization genes requires a pleiotropic transcriptional regulator necessary for survival in the mammalian gut. Genomic analysis predicts that this paradigm is broadly applicable to the breakdown of other polysaccharides in both B. thetaiotaomicron and other gut Bacteroides spp. The uncovered mechanism enables regulation of polysaccharide utilization genes in response to both the polysaccharide and its breakdown products.
  
  
  
  Breakdown of complex polysaccharides derived from "dietary fiber" is achieved by the mammalian gut microbiota. This breakdown creates a critical nutrient source for both the microbiota and its mammalian host. Because the availability of individual polysaccharides fluctuates with variations in the host diet, members of the microbiota strictly control expression of polysaccharide utilization genes. Our findings define a regulatory architecture that controls the breakdown of a polysaccharide by a gut bacterium in response to three distinct signals. This architecture integrates perception of a complex polysaccharide and its monomeric constituent as well as feedback of central metabolism. Moreover, it is broadly applicable to several prominent members of the mammalian gut microbiota. The identified regulatory strategy may contribute to the abundance of gut Bacteroides, despite fluctuations in the host diet.
authors.affiliation: Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA Yale Microbial Diversity Institute, West Haven, Connecticut, USA.
authors.forename: Nathan D
authors.initials: ND
authors.lastname: Schwalm
authors.affiliation: Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA Yale Microbial Diversity Institute, West Haven, Connecticut, USA.
authors.forename: Guy E
authors.initials: GE
authors.lastname: Townsend
authors.affiliation: Department of Microbial Pathogenesis, Yale School of Medicine, New Haven, Connecticut, USA Yale Microbial Diversity Institute, West Haven, Connecticut, USA eduardo.groisman@yale.edu.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Groisman
mesh_terms: D001089:Arabinose / Q000378:metabolism; D000070077:Bacteroides thetaiotaomicron / Q000378:metabolism*; D019295:Computational Biology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial / Q000187:drug effects*; D053263:Gene Regulatory Networks; D016680:Genome, Bacterial; D006868:Hydrolysis; D011134:Polysaccharides / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D011134:Polysaccharides; D012097:Repressor Proteins; D014157:Transcription Factors; C030080:araban; D001089:Arabinose