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.

[1]  A. Nelson,et al.  Cloning, over-expression, purification, and characterisation of N-acetylneuraminate synthase from Streptococcus agalactiae. , 2003, Protein expression and purification.

[2]  Carmen Buchrieser,et al.  Genome sequence of Streptococcus agalactiae, a pathogen causing invasive neonatal disease , 2002, Molecular microbiology.

[3]  Ian T. Paulsen,et al.  Complete genome sequence and comparative genomic analysis of an emerging human pathogen, serotype V Streptococcus agalactiae , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[4]  C. Rubens,et al.  CpsK of Streptococcus agalactiae exhibits α2,3‐sialyltransferase activity in Haemophilus ducreyi , 2002, Molecular microbiology.

[5]  S. Iijima,et al.  Molecular characterization of a novel beta1,3-galactosyltransferase for capsular polysaccharide synthesis by Streptococcus agalactiae type Ib. , 2002, Journal of biochemistry.

[6]  G. Glusman,et al.  Visualizing large-scale genomic sequences , 2001, IEEE Engineering in Medicine and Biology Magazine.

[7]  D. Kasper,et al.  Functional Analysis in Type Ia Group B Streptococcusof a Cluster of Genes Involved in Extracellular Polysaccharide Production by Diverse Species of Streptococci* , 2001, The Journal of Biological Chemistry.

[8]  Michael,et al.  Structure and Immunochemistry of an Oligosaccharide Repeating Unit of the Capsular Polysaccharide of Type I 11 Group B Streptococcus , 2001 .

[9]  H. Yim,et al.  The Serotype of Type Ia and III Group B Streptococci Is Determined by the Polymerase Gene within the Polycistronic Capsule Operon , 2000, Journal of bacteriology.

[10]  Doron Lancet,et al.  GESTALT: a workbench for automatic integration and visualization of large-scale genomic sequence analyses , 2000, Bioinform..

[11]  S. Iijima,et al.  Molecular Characterization of Type-Specific Capsular Polysaccharide Biosynthesis Genes of Streptococcus agalactiae Type Ia , 1999, Journal of bacteriology.

[12]  M. Lipsitch Bacterial vaccines and serotype replacement: lessons from Haemophilus influenzae and prospects for Streptococcus pneumoniae. , 1999, Emerging infectious diseases.

[13]  J. Yother Common themes in the genetics of streptococcal capsular polysaccharides , 1999 .

[14]  J. Goldberg Genetics of Bacterial Polysaccharides , 1999 .

[15]  W R Pearson,et al.  Comparison of DNA sequences with protein sequences. , 1997, Genomics.

[16]  Thomas L. Madden,et al.  Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. , 1997, Nucleic acids research.

[17]  M. Kolkman,et al.  Functional Analysis of Glycosyltransferases Encoded by the Capsular Polysaccharide Biosynthesis Locus of Streptococcus pneumoniae Serotype 14* , 1997, The Journal of Biological Chemistry.

[18]  A. Bairoch,et al.  The PROSITE database, its status in 1997 , 1997, Nucleic Acids Res..

[19]  J. Brisson,et al.  Structural and Immunochemical Characterization of the Type VIII Group B Streptococcus Capsular Polysaccharide (*) , 1996, The Journal of Biological Chemistry.

[20]  M. Wessels,et al.  Characterization of cpsF and its product CMP‐N‐acetylneuraminic acid synthetase, a group B streptococcal enzyme that can function in K1 capsular polysaccharide biosynthesis in Escherichia coli , 1996, Molecular microbiology.

[21]  J. Thompson,et al.  Using CLUSTAL for multiple sequence alignments. , 1996, Methods in enzymology.

[22]  J. Brisson,et al.  Structural elucidation of the novel type VII group B Streptococcus capsular polysaccharide by high resolution NMR spectroscopy. , 1995, Carbohydrate research.

[23]  C. von Hunolstein,et al.  Immunochemistry of capsular type polysaccharide and virulence properties of type VI Streptococcus agalactiae (group B streptococci) , 1993, Infection and immunity.

[24]  D. Kasper,et al.  Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci , 1992, Infection and immunity.

[25]  J. Brisson,et al.  Structural determination and immunochemical characterization of the type V group B Streptococcus capsular polysaccharide. , 1991, The Journal of biological chemistry.

[26]  J. Fournier Capsular Polysaccharides of Staphylococcus aureus , 1990 .

[27]  D. Bitter‐Suermann,et al.  Interaction of meningococcal group B monoclonal antibody and its Fab fragment with alpha 2-8-linked sialic acid polymers: requirement of a long oligosaccharide segment for binding. , 1989, Molecular immunology.

[28]  J. Brisson,et al.  Structure of the capsular polysaccharide antigen of type IV group B Streptococcus , 1989 .

[29]  D. Kasper,et al.  A model of high-affinity antibody binding to type III group B Streptococcus capsular polysaccharide. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[30]  N. Saitou,et al.  The neighbor-joining method: a new method for reconstructing phylogenetic trees. , 1987, Molecular biology and evolution.

[31]  D. Kasper,et al.  Structure and immunochemistry of an oligosaccharide repeating unit of the capsular polysaccharide of type III group B Streptococcus. A revised structure for the type III group B streptococcal polysaccharide antigen. , 1987, The Journal of biological chemistry.

[32]  A. Cross,et al.  The role of capsular antigens in serum resistance and in vivo virulence of Escherichia coli , 1986 .

[33]  C. Jones Identification of the tetrasaccharide repeating-unit of the Streptococcus pneumoniae type 23 polysaccharide by high-field proton n.m.r. spectroscopy. , 1985, Carbohydrate research.

[34]  D. Kasper,et al.  Structure of native polysaccharide antigens of type Ia and type Ib group B Streptococcus. , 1983, Biochemistry.

[35]  D. Kasper,et al.  Structural determination of the capsular polysaccharide antigen of type II group B Streptococcus. , 1983, The Journal of biological chemistry.

[36]  D. Kasper,et al.  Capsular sialic acid prevents activation of the alternative complement pathway by type III, group B streptococci. , 1982, Journal of immunology.

[37]  D. Kasper,et al.  Conformational aspects critical to the immunospecificity of the type III group B streptococcal polysaccharide. , 1981, Biochemistry.

[38]  D. Kasper,et al.  Immunologic response of man to group B meningococcal polysaccharide vaccines. , 1972, The Journal of infectious diseases.

[39]  C. Howard,et al.  The virulence for mice of strains of Escherichia coli related to the effects of K antigens on their resistance to phagocytosis and killing by complement. , 1971, Immunology.