Structural and genetic diversity of group B streptococcus capsular polysaccharides

Abstract

Group B Streptococcus (GBS) is an important pathogen of neonates, pregnant women, and immunocompromised individuals. GBS isolates associated with human infection produce one of nine antigenically distinct capsular polysaccharides which are thought to play a key role in virulence. A comparison of GBS polysaccharide structures of all nine known GBS serotypes together with the predicted amino acid sequences of the proteins that direct their synthesis suggests that the evolution of serotype-specific capsular polysaccharides has proceeded through en bloc replacement of individual glycosyltransferase genes with DNA sequences that encode enzymes with new linkage specificities. We found striking heterogeneity in amino acid sequences of synthetic enzymes with very similar functions, an observation that supports horizontal gene transfer rather than stepwise mutagenesis as a mechanism for capsule variation. Eight of the nine serotypes appear to be closely related both structurally and genetically, whereas serotype VIII is more distantly related. This similarity in polysaccharide structure strongly suggests that the evolutionary pressure toward antigenic variation exerted by acquired immunity is counterbalanced by a survival advantage conferred by conserved structural motifs of the GBS polysaccharides.

FIG. 1.

PRU structures of the nine GBS serotypes. Arrows represent potential relationships between PRUs.

FIG. 2.

Sequence analysis of all nine GBS capsular serotypes. (A) CpsA to -E and CpsL as well as NeuB, -D, -A, and -C are conserved in all nine serotypes and are shown only in the type Ia capsule cluster. The color inside each arrow indicates the degree of similarity of the amino acid sequence to those encoded by other open reading frames. A gap was introduced between CpsH and CpsI to permit an alignment of corresponding open reading frames. (B) Alignment of cpsG genes from serotypes Ia, Ib, II, III, IV, V, VI, and VII. (C) Alignment of cpsK genes from all nine serotypes. Each column of color in panels B and C represents 1 base of the nucleotide sequence. Red, thymine; green, guanine; yellow, adenine; blue, cytosine. Arrows in panels B and C denote regions where nucleotide sequences diverge or converge (see the text for more details).

FIG. 3.

Assignment of gene function on the basis of previously published results and sequence comparisons. The colors of the arrows have the same meanings as those in Fig. 2. Question marks denote two required glycosyltransferases with proposed functions. However, the genes encoding these enzymes have not yet been identified.

FIG. 4.

Model of genetic recombination among serotypes Ia, Ib, III, and VI. Boxed genes denote sections that have recombined.

FIG. 5.

Phylogenetic reconstruction of glycosyltransferases from serotypes Ia, IV, V, and VII.

FIG. 6.

Phylogenetic reconstruction of CpsK genes of all nine serotypes.