Mosaicism in the alpha-like protein genes of group B streptococci

Members of a family of repeat-containing surface proteins of group B strept ococci (CBS) defined by the alpha C and Rib proteins exhibit size variabili ty and cross-reactivity and have been studied as potential vaccine componen ts. We report evidence of horizontal DNA transfer with subsequent recombina tion as a mechanism generating diversity within this antigen family. Alp2 a nd Alp3 are additional members of the alpha C protein family identified in strains of the emerging CBS serotypes V and VIII. Each contains an overall genetic organization highly similar to that of the alpha C and Rib proteins , including a tandem repeat region and conserved N- and C-terminal regions. Among different strains, protein size varies according to the number of ta ndem repeats within the corresponding gene. Unlike the alpha C and Rib prot eins, however, the newly described alpha-like proteins contain other region s, including one similar to the IgA-binding region of the GBS beta C protei n, a nontandem repeat region, and an isolated repeat highly homologous to t he alpha C repeat. Sequence analysis of the regions flanking the alpha C pr otein gene on a 13.7-kb insert reveals several ORFs that are likely to be i nvolved in basic metabolic pathways. Analysis of corresponding flanking reg ions in other GBS strains, including the parent strains of the newly descri bed alpha-like proteins, shows striking conservation among all strains stud ied. These findings indicate that the alpha-like proteins are encoded by mo saic variants at a single genomic locus and suggest that recombination afte r horizontal DNA transfer is a means of generating diversity within this pr otein family.