Group B streptococcus (GBS) is the most significant pathogen causing neonatal sepsis and meningitis. Approximately 12,000-15,000 infant deaths from invasive GBS infections occur annually; 20%-60% of survivors suffer serious sequelae. Of the five GBS serotypes, type III is responsible for the majority of early infections with meningitis and late infections with or without meningitis. The type III specific polysaccharide capsular antigen (TSA III) is considered to be a major virulence factor based on immunological and epidemiological data. To prove that TSA III encapsulation is a major virulence factor this investigation seeks to identify and characterize the organization, control, and function of the TSA III genes utilizing molecular genetic techniques. Specific mutation in TSA III gene expression will be derived by transposon insertional mutagenesis. The effect of TSA III mutations on virulence will be confirmed in a neonatal rat model. Cloning of chromosomal DNA from mutagenized GBS III strains will isolate the genes responsible for TSA III biosynthesis. Polypeptide gene products from cloned TSA III genes will be demonstrated in an E. coli minicell system and the genetic organization, structure and function of TSA III genes defined. TSA III polysaccharide antigens produced by E. coli will be compared to TSA III antigens from GBS by standard immunologic techniques. Direct proof of the role of TSA III in virulence is possible once the genetics of encapsulation are known. Knowledge of the molecular and genetic events controlling the synthesis, transport, and secretion of TSA III will provide a foundation for understanding its role in invasive neonatal GBS infections.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Unknown (R23)
Project #
1R23AI022498-01
Application #
3445698
Study Section
Bacteriology and Mycology Subcommittee 1 (BM)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1985-07-01
Budget End
1986-06-30
Support Year
1
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Seattle Children's Hospital
Department
Type
DUNS #
048682157
City
Seattle
State
WA
Country
United States
Zip Code
98105
Maruvada, Ravi; Prasadarao, Nemani V; Rubens, C E (2009) Acquisition of factor H by a novel surface protein on group B Streptococcus promotes complement degradation. FASEB J 23:3967-77