Abstract

Group B Streptococcus (GBS) is a major bacterial pathogen for human neonates. The polysaccharide capsule of GBS appears to be an important factor in virulence. Capsular type III is the most common serotype in invasive neonatal infections, and is particularly associated with meningitis. Previous work has suggested that the unique structural features of the type III capsule, especially its terminal side chain sialic acid residues, account for the pathogenic potential of type III GBS. The goal of this proposal is to study directly the role of the type III GBS capsular polysaccharide in pathogenesis of GBS infections through biochemical and immunologic analysis of genetically manipulated type III GBS organisms and their gene products. Genes involved in capsular biosynthesis will be cloned in E. coli and the cloned gene products characterized with regard to their role in capsular biosynthesis. Transposon mutagenesis will be used to produce phenotypically altered capsule mutants in the background of a virulent type III GBS strain. Mutant capsular antigens will be characterized structurally and immunologically, and the effects of particular phenotypic alterations will be assessed in terms of resistance of mutant strains to opsonophagocytosis in vitro, and virulence in animals.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI028040-03
Application #
3142352
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1990-01-01
Project End
1993-12-31
Budget Start
1992-01-01
Budget End
1993-12-31
Support Year
3
Fiscal Year
1992
Total Cost
Indirect Cost

  Institution

Name
Brigham and Women's Hospital
Department
Type
DUNS #
071723621
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Deng, L; Kasper, D L; Krick, T P et al. (2000) Characterization of the linkage between the type III capsular polysaccharide and the bacterial cell wall of group B Streptococcus. J Biol Chem 275:7497-504
Valentin, E; Ghomashchi, F; Gelb, M H et al. (2000) Novel human secreted phospholipase A(2) with homology to the group III bee venom enzyme. J Biol Chem 275:7492-6
Wessels, M R; Kasper, D L; Johnson, K D et al. (1998) Antibody responses in invasive group B streptococcal infection in adults. J Infect Dis 178:569-72
Wessels, M R (1997) Biology of streptococcal capsular polysaccharides. Soc Appl Bacteriol Symp Ser 26:20S-31S
Haft, R F; Wessels, M R; Mebane, M F et al. (1996) 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. Mol Microbiol 19:555-63
Wessels, M R; Paoletti, L C; Pinel, J et al. (1995) Immunogenicity and protective activity in animals of a type V group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine. J Infect Dis 171:879-84
Wessels, M R; Butko, P; Ma, M et al. (1995) Studies of group B streptococcal infection in mice deficient in complement component C3 or C4 demonstrate an essential role for complement in both innate and acquired immunity. Proc Natl Acad Sci U S A 92:11490-4
Rubens, C E; Haft, R F; Wessels, M R (1995) Characterization of the capsular polysaccharide genes of group B streptococci. Dev Biol Stand 85:237-44
Haft, R F; Wessels, M R (1994) Characterization of CMP-N-acetylneuraminic acid synthetase of group B streptococci. J Bacteriol 176:7372-4
Marques, M B; Kasper, D L; Shroff, A et al. (1994) Functional activity of antibodies to the group B polysaccharide of group B streptococci elicited by a polysaccharide-protein conjugate vaccine. Infect Immun 62:1593-9

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