Group B Streptococcus (Streptococcus agalactiae) remains a major cause of death and serious illness in newborn babies and has emerged as an important pathogen in immunocompromised adults. Our work on this pathogen has focused on a group of immunologically important surface proteins, the prototype for which is the alpha C protein. These protective surface proteins are characterized by the presence of long tandem repeating subunits. Variation in the number of tandem repeats gives rise to antigenic variation and permits escape mutation. During the first funding period for this project, we established that deletions of tandem repeats within the alpha C protein gene give rise to changes in the antigenic structure of the protein, alters its immunogenicity, and affects its positioning on the bacterial surface. These changes underlie the ability of group B streptococci to escape from host immunity to this antigen. New data show a role for the alpha C and alpha-like proteins in binding and invasion of epithelial cells. In this renewal, we will examine the alpha C protein with respect to its adaptive advantage for group B streptococci. Specifically, we will examine mechanisms for regulation of expression of the proteins and study how the proteins mediate the interaction of streptococci with host epithelial cells. These studies will lead to advances in the understanding of group B streptococcal immunity, further the effort to employ these proteins in vaccines for the prevention of group B streptococcal infection, and enhance the understanding of pathogenesis at the most fundamental level.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI038424-07
Application #
6706201
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Rubin, Fran A
Project Start
1997-03-01
Project End
2006-01-31
Budget Start
2004-02-01
Budget End
2005-01-31
Support Year
7
Fiscal Year
2004
Total Cost
$343,330
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
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Klinzing, David C; Madoff, Lawrence C; Puopolo, Karen M (2009) Genomic analysis identifies a transcription-factor binding motif regulating expression of the alpha C protein in Group B Streptococcus. Microb Pathog 46:315-20
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Yang, Hsiao-Hui; Mascuch, Samantha J; Madoff, Lawrence C et al. (2008) Recombinant group B Streptococcus alpha-like protein 3 is an effective immunogen and carrier protein. Clin Vaccine Immunol 15:1035-41