Streptococcal protein Rib and related proteins: a family of repetitive surface proteins that elicit protective immunity

ABSTRACT

Streptococci constitute a heterogeneous group of Gram-positive bacteria, divided into different serological groups on the basis of antigenic differences in a cell wall-associated carbohydrate. This thesis describes related surface proteins expressed by bacteria in two of these groups, the group B streptococcus (GBS) and the group A streptococcus (GAS). GBS is an encapsulated bacterium that is the major cause of invasive bacterial infections in the neonatal period. We have identified and purified a novel cell surface protein, Rib, which is expressed by many GBS strains causing invasive infections. Protein Rib confers protective immunity in a mouse model, making it of interest for analysis of pathogenetic mechanisms and for vaccine development. Sequence analysis demonstrated that the sequence of Rib is related to that of a previously described GBS protein, the alpha protein. Both of these proteins have exceptionally long signal peptides and their sequences are extremely repetitive. Although the two proteins show extensive amino acid residue identity they do not cross-react immunologically. Rib and alpha share several properties i.e. size variation between strains and protease resistance, and they show a characteristic laddering pattern when analyzed in Western blots, due to hydrolysis of acid-labile Asp-Pro bonds. These data show that the Rib and alfa proteins are members of a novel family of streptococcal surface proteins with unusual repetitive structure. R28 is a surface protein expressed by some strains of group A streptococci (Streptococcus pyogenes). The R28 protein cross-reacts immunologically with the Rib protein of GBS, and sequence analysis showed that R28 is a member of the same family of repetitive proteins as Rib and alpha. R28 promotes adhesion to human epithelial cells, and has the important property to elicit protective immunity. Interestingly, the R28 and Rib proteins, which are expressed by different bacterial species, confer cross-protection, i.e. immunization with R28 protects against Rib-expressing strains, and vice versa.