title: Coordinate regulation of glycan degradation and polysaccharide capsule biosynthesis by a prominent human gut symbiont.
abstract: Bacteria in the distal human gut have evolved diverse abilities to metabolize complex glycans, including the capacity to degrade these compounds as nutrients and to assemble their component sugars into new polymers such as extracellular capsules. The human gut bacterium Bacteroides thetaiotaomicron is well endowed with the ability to metabolize both host- and diet-derived glycans. Its genome contains 88 different polysaccharide utilization loci (PULs) for complex glycan catabolism and eight different gene clusters for capsular polysaccharide biosynthesis. Here, we investigate one of the prominent mechanisms by which this gut symbiont regulates many PULs involved in host mucin O-glycan degradation; namely, transcriptional regulation via the concerted interactions of cell-envelope-localized TonB-dependent transporters, extra-cytoplasmic function sigma factors and anti-sigma factors, which participate together in a regulatory pathway termed trans-envelope signaling. Unexpectedly, we found that several different trans-envelope signaling switches involved in PUL-mediated O-glycan degradation also modulate capsular polysaccharide synthesis. A novel regulatory pathway, which is dependent on expression of O-glycan-targeting outer membrane proteins, governs this coordinated regulation of glycan catabolism and capsule synthesis. This latter finding provides a new link in the dynamic interplay between complex glycan metabolism, microbial physiology, and host responses that occurs during colonization of the gut.
authors.affiliation: Center for Genome Sciences, Washington University School of Medicine, St. Louis, Missouri 63108, USA.
authors.forename: Eric C
authors.initials: EC
authors.lastname: Martens
authors.forename: Robyn
authors.initials: R
authors.lastname: Roth
authors.forename: John E
authors.initials: JE
authors.lastname: Heuser
authors.forename: Jeffrey I
authors.initials: JI
authors.lastname: Gordon
mesh_terms: D000328:Adult; D016667:Bacterial Capsules / Q000235:genetics / Q000378:metabolism; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics* / Q000378:metabolism*; D001439:Bacteroides / Q000235:genetics* / Q000378:metabolism*; D025461:Feedback, Physiological / Q000502:physiology; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D005798:Genes, Bacterial / Q000502:physiology; D016680:Genome, Bacterial; D006801:Humans; D007422:Intestines / Q000382:microbiology; D020411:Oligonucleotide Array Sequence Analysis; D011134:Polysaccharides / Q000378:metabolism*; D011135:Polysaccharides, Bacterial / Q000096:biosynthesis*; D011401:Promoter Regions, Genetic / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology; D013559:Symbiosis / Q000502:physiology; D020798:Two-Hybrid System Techniques
chemical_list: D001425:Bacterial Outer Membrane Proteins; D011134:Polysaccharides; D011135:Polysaccharides, Bacterial