title: Structural and genetic diversity of group B streptococcus capsular polysaccharides.
abstract: Group B Streptococcus (GBS) is an important pathogen of neonates, pregnant women, and immunocompromised individuals. GBS isolates associated with human infection produce one of nine antigenically distinct capsular polysaccharides which are thought to play a key role in virulence. A comparison of GBS polysaccharide structures of all nine known GBS serotypes together with the predicted amino acid sequences of the proteins that direct their synthesis suggests that the evolution of serotype-specific capsular polysaccharides has proceeded through en bloc replacement of individual glycosyltransferase genes with DNA sequences that encode enzymes with new linkage specificities. We found striking heterogeneity in amino acid sequences of synthetic enzymes with very similar functions, an observation that supports horizontal gene transfer rather than stepwise mutagenesis as a mechanism for capsule variation. Eight of the nine serotypes appear to be closely related both structurally and genetically, whereas serotype VIII is more distantly related. This similarity in polysaccharide structure strongly suggests that the evolutionary pressure toward antigenic variation exerted by acquired immunity is counterbalanced by a survival advantage conferred by conserved structural motifs of the GBS polysaccharides.
authors.affiliation: Division of Infectious Diseases, Children's Hospital, University of Washington, Seattle, WA 98109, USA. craig.rubens@seattlechildrens.org
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Cieslewicz
authors.forename: Donald
authors.initials: D
authors.lastname: Chaffin
authors.forename: Gustavo
authors.initials: G
authors.lastname: Glusman
authors.forename: Dennis
authors.initials: D
authors.lastname: Kasper
authors.forename: Anup
authors.initials: A
authors.lastname: Madan
authors.forename: Stephani
authors.initials: S
authors.lastname: Rodrigues
authors.forename: Jessica
authors.initials: J
authors.lastname: Fahey
authors.forename: Michael R
authors.initials: MR
authors.lastname: Wessels
authors.forename: Craig E
authors.initials: CE
authors.lastname: Rubens
mesh_terms: D016667:Bacterial Capsules / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002240:Carbohydrate Sequence; D022761:Gene Transfer, Horizontal; D014644:Genetic Variation; D008969:Molecular Sequence Data; D005810:Multigene Family; D010802:Phylogeny; D011995:Recombination, Genetic; D017422:Sequence Analysis, DNA; D012703:Serotyping; D013290:Streptococcal Infections; D013292:Streptococcus agalactiae / Q000145:classification* / Q000235:genetics
chemical_list: D001426:Bacterial Proteins