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.
