title: Phase-variable expression of a family of glycoproteins imparts a dynamic surface to a symbiont in its human intestinal ecosystem.
abstract: The recent report of the synthesis of glycoproteins by the abundant intestinal symbionts Bacteroides showed that these organisms use a novel bacterial enzyme to decorate their surfaces with a sugar residue derived from their environment. As a first step in understanding the importance of these glycoproteins to the bacteria and to the bacterial-host symbiosis, we identified and characterized the abundant glycoproteins of Bacteroides distasonis (proposed reclassification as Parabacteroides distasonis) [Sakamoto M, Benno Y (2006) Int J Syst Evol Microbiol 56:1599-1605]. Using lectin-affinity purification followed by tandem mass spectrometry, we identified a family of at least nine glycoproteins, similar only to the S-layer glycoproteins of Tannerella forsythia. Analysis of one of these purified glycoproteins demonstrated that the glycan is primarily a polymer of xylose, a monosaccharide rarely found in bacterial glycans. Even more unexpected was the finding that seven of nine of the glycoprotein promoters undergo DNA inversion, a process that we show is active in their endogenous human environment. Using cross-species functional assays, we show that a single serine family site-specific recombinase globally mediates the inversions of these glycoprotein promoters. This regulatory mechanism is similar to that of the Bacteroides fragilis capsular polysaccharides and establishes DNA inversion as a general and ancient means of regulation of glycan-containing surface molecules of these important human intestinal symbionts.
authors.affiliation: Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA.
authors.forename: C Mark
authors.initials: CM
authors.lastname: Fletcher
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Coyne
authors.forename: David L
authors.initials: DL
authors.lastname: Bentley
authors.forename: Otto F
authors.initials: OF
authors.lastname: Villa
authors.forename: Laurie E
authors.initials: LE
authors.lastname: Comstock
mesh_terms: D001426:Bacterial Proteins / Q000235:genetics / Q000302:isolation & purification; D001439:Bacteroides / Q000737:chemistry / Q000235:genetics*; D017753:Ecosystem; D005786:Gene Expression Regulation; D006023:Glycoproteins / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D007422:Intestines / Q000382:microbiology*; D011401:Promoter Regions, Genetic / Q000235:genetics; D013559:Symbiosis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D006023:Glycoproteins