title: A Phase-Variable Surface Layer from the Gut Symbiont Bacteroides thetaiotaomicron.
abstract: The capsule from Bacteroides, a common gut symbiont, has long been a model system for studying the molecular mechanisms of host-symbiont interactions. The Bacteroides capsule is thought to consist of an array of phase-variable polysaccharides that give rise to subpopulations with distinct cell surface structures. Here, we report the serendipitous discovery of a previously unknown surface structure in Bacteroides thetaiotaomicron: a surface layer composed of a protein of unknown function, BT1927. BT1927, which is expressed in a phase-variable manner by ~1:1,000 cells in a wild-type culture, forms a hexagonally tessellated surface layer. The BT1927-expressing subpopulation is profoundly resistant to complement-mediated killing, due in part to the BT1927-mediated blockade of C3b deposition. Our results show that the Bacteroides surface structure is capable of a far greater degree of structural variation than previously known, and they suggest that structural variation within a Bacteroides species is important for productive gut colonization.
  
  
  OBJECTIVE
  Many bacterial species elaborate a capsule, a structure that resides outside the cell wall and mediates microbe-microbe and microbe-host interactions. Species of Bacteroides, the most abundant genus in the human gut, produce a capsule that consists of an array of polysaccharides, some of which are known to mediate interactions with the host immune system. Here, we report the discovery of a previously unknown surface structure in Bacteroides thetaiotaomicron. We show that this protein-based structure is expressed by a subset of cells in a population and protects Bacteroides from killing by complement, a component of the innate immune system. This novel surface layer protein is conserved across many species of the genus Bacteroides, suggesting an important role in colonization and host immune modulation.
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California, USA Graduate Group in Infectious Diseases and Immunity, School of Public Health, University of California, Berkeley, Berkeley, California, USA.
authors.forename: Mao
authors.initials: M
authors.lastname: Taketani
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Mohamed S
authors.initials: MS
authors.lastname: Donia
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California, USA.
authors.forename: Amy N
authors.initials: AN
authors.lastname: Jacobson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Lambris
authors.affiliation: Department of Bioengineering and Therapeutic Sciences and California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California, USA fischbach@fischbachgroup.org.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Fischbach
mesh_terms: D001439:Bacteroides / Q000737:chemistry* / Q000235:genetics; D001770:Blood Bactericidal Activity; D003179:Complement C3b / Q000037:antagonists & inhibitors; D041981:Gastrointestinal Tract / Q000382:microbiology*; D006801:Humans; D057131:Immune Evasion; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics
chemical_list: D008562:Membrane Glycoproteins; C055764:S-layer proteins; D003179:Complement C3b