Chapter 21 : Type III Capsular Polysaccharide of Group B Streptococci: Role in Virulence and the Molecular Basis of Capsule Expression

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Group B streptococci (GBS) are weakly beta-hemolytic, facultatively anaerobic, gram-positive cocci which have emerged over the past 50 years as the most common cause of neonatal pneumonia, sepsis, and meningitis in the United States, western Europe, and some developing countries. The type III capsular polysaccharide is a high-molecular-weight polymer composed of repeating pentasaccharide subunits containing a trisaccharide backbone of galactose, glucose, and N-acetylglucosamine with a side chain of galactose and a terminal sialic acid moiety. In epidemiological studies, a correlation was observed between newborns with antibody to the sialylated capsule and protection from infection, which is in contrast to the case for infants who lacked antibody or who had antibody to the desialylated polysaccharide. Subcutaneous injection of the acapsular or asialo mutants into neonatal rats resulted in similar 50% lethal doses that were at least 2 orders of magnitude higher than those observed for the parent strain. The genetic characterization of complex polysaccharide production by gramnegative bacteria has proceeded more quickly because of advances in the molecular technology available for these organisms. Molecular analysis of the genes involved in GBS capsule biosynthesis should provide an understanding of complex polysaccharide biosynthesis and transport in gram-positive organisms. Similar studies investigating capsule synthesis by and are being pursued.

Citation: Rubens C. 1994. Type III Capsular Polysaccharide of Group B Streptococci: Role in Virulence and the Molecular Basis of Capsule Expression, p 327-339. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch21

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Sialic Acids
Cell Wall
Streptococcus pneumoniae
Streptococcus pyogenes
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Figure 1

Repeating unit structure of native and asialo type III capsular polysaccharide.

Citation: Rubens C. 1994. Type III Capsular Polysaccharide of Group B Streptococci: Role in Virulence and the Molecular Basis of Capsule Expression, p 327-339. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch21
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Image of Figure 2.
Figure 2.

The 30-kb region of representative type III GBS chromosome. E, RI sites; X, sites; *, RI RFLP seen in some type III and all type Ia strains analyzed to date. Numbers above the map indicate the sizes of the RI fragments (in kilobases). Inverted triangles are Tn or Tn transposon insertion sites in type III GBS capsule mutants discussed in the text. Open arrows indicate open reading frames, with the orientation of transcription, the gene letter designation, and sizes (in kilodaltons) indicated.

Citation: Rubens C. 1994. Type III Capsular Polysaccharide of Group B Streptococci: Role in Virulence and the Molecular Basis of Capsule Expression, p 327-339. In Miller V, Kaper J, Portnoy D, Isberg R (ed), Molecular Genetics of Bacterial Pathogenesis. ASM Press, Washington, DC. doi: 10.1128/9781555818340.ch21
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1. Adamkin, D.,, B. A. Stitzel,, J. Urmson,, M. L. Farnett,, E. Post,, and R. Spitzer. 1978. Activity of the alternative pathway of complement in the newborn infant. J. Pediatr. 93:604608.
2. Albright, C. F.,, P. Orlean,, and P. W. Robbins. 1989. A 13-amino acid peptide in three yeast glycosyltransferases may be involved in dolichol recognition. Proc. Natl. Acad. Sci. USA 86: 73667369.
3. Anderson, D. C.,, M. S. Edwards,, and C. J. Baker. 1980. Luminol-enhanced chemiluminescence for evaluation of type III group B streptococcal opsonins in human sera. J. Infect. Dis. 141: 370381.
4. Anthony, B. F. 1976. Immunity to the group B streptococci: interaction of serum and macrophages with types Ia, Ib, and Ic. J. Exp. Med. 143:11861198.
5. Avery, O. T.,, C. M. MacLeod,, and M. McCarty. 1944. Studies on the chemical nature of the substance inducing transformation of pneumococcal types. Induction of transformation by a desoxyribonucleic acid fraction isolated from pneumococcus type III. J. Exp. Med. 79:137158.
6. Baker, C. J.,, and M. S. Edwards,. 1990. Group B streptococcal infections, p. 742811. In J. S. Remington, and J. O. Klein (ed.), Infectious Diseases of the Fetus and Newborn Infant. The W. B. Saunders Co., Philadelphia.
7. Baker, C. J.,, and D. L. Kasper. 1976. Correlation of maternal antibody deficiency with susceptibility to neonatal group B streptococcal infection. N. Engl. J. Med. 294:753756.
8. Balcklow, R. S.,, and L. Warren. 1962. The biosynthesis of sialic acids by Neisseria meningitidis. J. Biol. Chem. 237:35203526.
9. Baltimore, R. S.,, D. L. Kasper,, C. J. Baker,, and D. K. Goroff. 1977. Antigenic specificity of opsonophagocytic antibodies in rabbit antisera to group B streptococci. J. Immunol. 118:673678.
10. Bernheimer, H. P.,, and I. E. Wermundsen. 1972. Homology in capsular transformation fractions in Pneumococcus. Mol. Gen. Genet. 116:6883.
11. Boulnois, G. J.,, and K. Jann. 1989. Bacterial polysaccharide capsule synthesis, export and evolution of structural diversity. Mol. Microbiol. 3:18191823.
12. Clarke, B. R.,, and C. Whitfield. 1992. Molecular cloning of the rfb region of Klebsiella pneumoniae serotype Ol:K20: the rfb gene cluster is responsible for synthesis of the D-galactan IO polysaccharide. J. Bacteriol. 174:46144621.
13. d'Ascenzi, S.,, C. von Hunolstein,, M. Dentin),, G. Alfarone,, V. Crescenzi,, and G. Orefici,. 1992. Characterization of group B Streptococcus type capsular polysaccharides, p. 458460. In G. Orefici (ed.), New Perspectives on Streptococci and Streptococcal Infections. Proceedings of the XI Lancefield International Symposium. Gustav Fisher Verlag, New York.
14. Dawson, M. H.,, and R. H. P. Sia. 1931. In vitro transformation of pneumococcal types. A technique for inducting transformation of pneumococcal types in vitro. J. Exp. Med. 54:681699.
15. Dougherty, B. A.,, and I. van de Ryn. 1992. Molecular characterization of a locus required for hyaluronic acid capsule production in group A streptococci. J. Exp. Med. 175:12911299.
16. Edwards, M. S.,, C. J. Baker,, and D. L. Kasper. 1979. Opsonic specificity of human antibody to the type III polysaccharide of group B Streptococcus. J. Infect. Dis. 140:10041008.
17. Edwards, M. S.,, D. L. Kasper,, H. J. Jennings,, C. J. Baker,, and A. Nicholson-Weller. 1982. Capsular sialic acid prevents activation of the alternative complement pathway by type III, group B streptococci. J. Immunol. 128:12781283.
18. Edwards, M. S.,, A. Nicholson-Weller,, C. J. Baker,, and D. L. Kasper. 1980. The role of specific antibody in alternative pathway-mediated opsonophagocytosis of type III, group B Streptococcus. J. Exp. Med. 151:12751287.
19. Edwards, M. S.,, M. A. Rench,, A. A. M. Haffer,, M. A. Murphy,, M. M. Desmond,, and C. J. Baker. 1985. Long-term sequelae of group B streptococcal meningitis in infants. J. Pediatr. 106:717722.
20. Effrussi-Taylor, H. 1951. Genetic aspects of transformation of pneumococci. Cold Spring Harbor Symp. Quant. Biol. 16:445456.
21. Farley, M. M.,, R. C. Harvey,, T. Stull,, J. D. Smith,, A. Schuchat,, J. D. Wenger,, and D. S. Stephens. 1993. A population-based assessment of invasive disease due to group B streptococcus in nonpregnant adults. N. Engl. J. Med. 328:18071811.
22. Frosch, M.,, C. Weisgeber,, and T. F. Meyer. 1989. Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neisseria meningitidis group B. Proc. Natl. Acad. Sci. USA 86:16991673.
23. Gibson, R. L.,, M. K. Lee,, C. Soderland,, E. Y. Chi,, and C. E. Rubens. 1993. Group B streptococci invade endothelial cells: type III capsular polysaccharide attenuates invasion. Infect. Immun. 61: 478485.
24. Glucksmann, M. A.,, T. L. Reuber,, and G. C. Walker. 1993. Genes needed for the modification, polymerization, export, and processing of succinoglycan by Rhizobium meliloti: a model for succi-noglycan biosynthesis. J. Bacteriol. 175:70457055.
25. Gray, B. M.,, and D. G. Pritchard,. 1992. Phase variation in the pathogenesis of group B streptococcal infections, p. 452454. In G. Orefici (ed.), New Perspectives on Streptococci and Streptococcal Infections. Proceedings of the XI Lancefield International Symposium. Gustav Fisher Verlag, New York.
26. Griffith, F. 1928. The significance of pneumococcal types. J. Hyg. 27:119159.
27. Haft, R.,, M. Mebane,, M. Wessels,, and C. E. Rubens. Unpublished data.
28. Hakansson, S.,, A. Bergholm,, S. E. Holm,, B. Wagner,, and M. Wagner. 1988. Properties of high and low density subpopulations of group B streptococci: enhanced virulence of the low density variant. Microb. Pathog. 5:345355.
29. Hakansson, S.,, S. E. Holm,, and M. Wagner. 1987. Density profile of group B streptococci, type III, and its possible relation to enhanced virulence. J. Clin. Microbiol. 25:714718.
30. Higgins, C. F. 1993. ABC transporters: from microorganisms to man. Annu. Rev. Cell Biol. 8: 67113.
31. Hill, H. R.,, A. O. Shigeoka,, R. T. Hall,, and V. G. Hemming. 1979. Neonatal cellular and humoral immunity to group B streptococci. Pediatrics S64:787794.
32. Hostetter, M. K. 1986. Serotypic variations among virulent pneumococci in deposition and degradation of covalently bound C3b: implications for phagocytosis and antibody production. J. Infect. Dis. 153:682692.
33. Hulse, M. L.,, S. Smith,, E. Y. Chi,, A. Pham,, and C. E. Rubens. 1993. The effect of type III group B streptococcal capsular polysaccharide on invasion of respiratory epithelial cells. Infect. Immun. 61:48354841.
34.Institute of Medicine, National Academy of Sciences. 1985. New vaccine development: establishing priorities, p. 242439, appendix P. In Diseases of Importance in the United States, vol. 1. National Academy Press, Washington, D.C..
35. Jarvis, G. A.,, and N. A. Vedros. 1987. Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation. Infect. Immun. 55:174180.
36. Jelinkova, J.,, and J. Motlova. 1985. The nomenclature of GBS. Antibiot. Chemother. 35:4952.
37. Jiang, X. M.,, B. Neal,, F. Santiago,, S. J. Lee,, L. K. Romana,, and P. R. Reeves. 1991. Structure and sequence of the rbf (O antigen) gene cluster of Salmonella serovar typhimurium (strains LT2). Mol. Microbiol. 5:695713.
38. Kasper, D. L.,, C. J. Baker,, R. S. Baltimore,, J. H. Crabb,, G. Schiffman,, and H. J. Jennings. 1979. Immunodeterminant specificity of human immunity to type III group B streptococcus. J. Exp. Med. 149:327339.
39. Kroll, J. S.,, I. Hopkins,, and E. R. Moxon. 1988. Capsule loss in H. influenzae type b occurs by recombination-mediated disruption of a gene essential for polysaccharide export. Cell 53:347356.
40. Kroll, J. S.,, B. M. Loynds,, and E. R. Moxon. 1991. The Haemophilus influenzae capsulation gene cluster: a compound transposon. Mol. Microbiol. 5:15491560.
41. Kuypers, J. M.,, L. M. Heggen,, and C. E. Rubens. 1989. Molecular analysis of a region of the group B Streptococcus chromosome involved in type III capsule expression. Infect. Immun. 57: 30583065.
42. Liu, D.,, A. M. Haase,, L. Lindqvist,, A. A. Lindberg,, and P. R. Reeves. 1993. Glycosyl transferases of O-antigen biosynthesis in Salmonella enterica: identification and characterization of transferase genes of groups B, C2, and El. J. Bacteriol. 175:34083413.
43. Marques, M. B.,, D. L. Kasper,, M. K. Pangburn,, and M. R. Wessels. 1992. Prevention of C3 deposition by capsular polysaccharide is a virulence mechanism of type III group B streptococci. Infect. Immun. 60:39863993.
44. Martin, T. R.,, J. T. Ruzinski,, C. E. Rubens,, E. Y. Chi,, and C. B. Wilson. 1992. The effect of type-specific polysaccharide capsule on the clearance of group B streptococci from the lungs of infant and adult rats. J. Infect. Dis. 165:306314.
45. Merker, R. I.,, and F. A. Troy. 1990. Biosynthesis of the polysialic acid capsule in Escherichia coli Kl. Cold inactivation of sialic acid synthase regulates capsule expression below 20°C. Glycobiology 1:93100.
46. Muller, P.,, M. Keller,, W. M. Weng,, J. Quandt,, W. Arnold,, and A. Punier. 1993. Genetic analysis of the Rhizobium meliloti exoYFQ operon: ExoY is homologous to sugar transferases and ExoQ represents a transmembrane protein. Am. Phytopathol. Soc. 6:5565.
47. Ravin, A. W. 1960. Linked mutations borne by deoxyribonucleic acid controlling the synthesis of capsular polysaccharide in pneumococcus. Genetics 45:13871403.
48. Reuber, T. L.,, and G. C. Walker. 1993. Biosynthesis of succinoglycan, a symbiotically important exopolysaccharide of Rhizobium meliloti. Cell 74:269280.
49. Roberts, I.,, R. Mountford,, N. High,, D. Bitter-Suermann,, K. Jann,, K. Timmls,, and G. Boulnois. 1986. Molecular cloning and analysis of genes for production of K5, K7, K12, and K92 capsular polysaccharides in Escherichia coli. J. Bacteriol. 168:12281233.
50. Rubens, C. E. Unpublished data.
51. Rubens, C. E.,, L. M. Heggen,, R. F. Haft,, and M. R. Wessels. 1993. Identification of cpsD, a gene essential for type III capsule expression in group B streptococci. Mol. Microbiol. 8:843855.
52. Rubens, C. E.,, J. M. Kuypers,, L. M. Heggen,, D. L. Kasper,, and M. R. Wessels,. 1991. Molecular analysis of the group B streptococcal capsule genes, p. 179183. In G. M. Dunny,, P. P. Cleary,, and L. L. McKay (ed.), Genetics and Molecular Biology of Streptococci, Lactococci, and Enterococci. American Society for Microbiology, Washington, D.C..
53. Rubens, C. E.,, M. R. Wessels,, L. M. Heggen,, and D. L. Kasper. 1987. Transposon mutagenesis of group B streptococcal type III capsular polysaccharide: correlation of capsule expression with virulence. Proc. Natl. Acad. Sci. USA 84:72087212.
54. Rubens, C. E.,, H. V. Raff,, J. C. Jackson,, E. Y. Chi,, J. T. Bielitzki,, and S. L. Hillier. 1991. Pathophysiology and histopathology of group B streptococcal sepsis in Macaca nemestrina primates induced after intraamniotic inoculation: evidence for bacterial cellular invasion. J. Infect. Dis. 164:320330.
55. Rubens, C. E.,, S. Smith,, M. Hulse,, E. Y. Chi,, and G. van Belle. 1992. Respiratory epithelial cell invasion by group B streptococci. Infect. Immun. 60:51575163.
56. Shigeoka, A. O.,, R. T. Hall,, V. G. Hemming,, C. O. Allred,, and H. R. Hill. 1978. Role of antibody and complement in opsonization of group B streptococci. Infect. Immun. 21:3440.
57. Silver, R. P.,, P. Annunziato,, M. S. Pavelka,, R. P. Pigeon,, L. F. Wright,, and D. E. Wunder,. 1993. Genetic and molecular analyses of the polysialic acid cluster of Escherichia coli Kl, p. 5971. In J. Roth,, U. Rutishauser,, and F. A. Troy II (ed.), Polysialic Acid. Birkhauser Verlag, Basel.
58. Silver, R. P.,, C. W. Finn,, W. F. Vann,, W. Aaronson,, R. Schneerson,, P. J. Kretschmer,, and C. F. Garon. 1981. Molecular cloning of the Kl capsular polysaccharide genes of E. coli. Nature (London) 289:696698.
59. Steenbergen, S. M.,, T. J. Wrona,, and E. R. Vimr. 1992. Functional analysis of the sialyltransferase complexes in Escherichia coli Kl and K92. J. Bacteriol. 174:10991108.
60. Stewardson-Krieger, P. B.,, K. Albrandt,, T. Nevin,, R. R. Kretschmer,, and S. P. Gotoff. 1977. Perinatal immunity to group B B-hemolytic Streptococcus type la. J. Infect. Dis. 136:649654.
61. St. Geme, J. W., III,, and S. Falkow. 1990. Haemophilus influenzae adheres to and enters cultured human epithelial cells. Infect. Immun. 58:40364044.
62. Stoolmiller, A. C.,, and A. Dorfman. 1969. The biosynthesis of hyaluronic acid by Streptococcus. J. Biol. Chem. 244:236246.
63. Sutherland, I. W. 1982. Biosynthesis of microbial exopolysaccharides. Adv. Microb. Physiol. 23: 79150.
64. Tamura, G.,, and C. Rubens. Host-bacterial interactions in pathogenesis of group B streptococcal infection. Curr. Opinions Infect. Dis., in press.
65. Troy, F. A. 1992. Polysialylation: from bacteria to brains. Glycobiology 2:523.
66. Troy, F. A.,, I. K. Vijay,, and N. Tesche. 1975. Role of undecaprenyl phosphate in synthesis of polymers containing sialic acid in Escherichia coli. J. Biol. Chem. 250:156163.
67. VanDtfk, W. C.,, H. A. Verbrugh,, M. E. Tol,, R. Peters,, and J. Verhoef. 1979. Role of Escherichia coli K capsular antigens during complement activation, C3 fixation and opsonization. Infect. Immun. 25:603609.
68. Vann, W. F.,, R. P. Silver,, C. Abeijon,, K. Chang,, W. Aaronson,, A. Sutton,, C. W. Finn,, W. Linder,, and M. Kotsatos. 1987. Purification, properties, and genetic location of Escherichia coli cytidine 5'-monophosphate N-acetylneuraminic acid synthetase. J. Biol. Chem. 262:1755617562.
69. Wald, E. R.,, I. Bergman,, H. B. Taylor,, D. Chiponis,, C. Porter,, and K. Kubek. 1986. Long-term outcome of group B streptococcal meningitis. Pediatrics 77:217221.
70. Walsh, J. A.,, and S. Hutchins. 1989. Group B streptococcal disease: its importance in the developing world and prospect for prevention with vaccines. Pediatr. Infect. Dis. J. 8:271276.
71. Watson, D. A.,, and D. M. Musher. 1990. Interruption of capsule production in Streptococcus pneumoniae serotype 3 by insertion of transposon Tn9/6. Infect. Immun. 58:31353138.
72. Wessels, M. R.,, R. F. Haft,, L. M. Heggen,, and C. E. Rubens. 1992. Identification of a genetic locus essential for capsule sialylation in type III group B streptococci. Infect. Immun. 60:392400.
73. Wessels, M. R.,, A. E. Moses,, J. M. Goldberg,, and T. J. DiCesare. 1991. Hyaluronic acid capsule is a virulence factor for mucoid group A streptococci. Proc. Natl. Acad. Sci. USA 88:83178321.
74. Wessels, M. R.,, C. E. Rubens,, V.-J. Benedi,, and D. L. Kasper. 1989. Definition of a bacterial virulence factor: sialylation of the group B streptococcal capsule. Proc. Natl. Acad. Sci. USA 86:89838987.
75. Wright, A. 1971. Mechanism of conversion of the Salmonella O antigen by bacteriophage e34. J. Bacteriol. 105:927936.
76. Yeung, M. K.,, and S. J. Mattingly. 1983. Isolation and characterization of type III group B streptococcal mutants defective in biosynthesis of the type-specific antigen. Infect. Immun. 42:141151.
77. Zangwill, K. M.,, A. Schuchat,, and J. Wenger. 1990. Group B streptococcal disease in the United States: report from a multistate active surveillance system. Morbid. Mortal. Weekly Rep. 41: 2532.
78. Zapata, G.,, W. F. Bann,, W. Aaronson,, M. S. Lewis,, and M. Moos. 1989. Sequence of the cloned Escherichia coli Kl CMP-N-acetylneuraminic acid synthetase gene. J. Biol. Chem. 264: 1476914774.

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