Genetic relatedness of the Streptococcus pneumoniae capsular biosynthetic loci

Abstract

Streptococcus pneumoniae (the pneumococcus) produces 1 of 91 capsular polysaccharides (CPS) that define the serotype. The cps loci of 88 pneumococcal serotypes whose CPS is synthesized by the Wzy-dependent pathway were compared with each other and with additional streptococcal polysaccharide biosynthetic loci and were clustered according to the proportion of shared homology groups (HGs), weighted for the sequence similarities between the genes encoding the shared HGs. The cps loci of the 88 pneumococcal serotypes were distributed into eight major clusters and 21 subclusters. All serotypes within the same serogroup fell into the same major cluster, but in six cases, serotypes within the same serogroup were in different subclusters and, conversely, nine subclusters included completely different serotypes. The closely related cps loci within a subcluster were compared to the known CPS structures to relate gene content to structure. The Streptococcus oralis and Streptococcus mitis polysaccharide biosynthetic loci clustered within the pneumococcal cps loci and were in a subcluster that also included the cps locus of pneumococcal serotype 21, whereas the Streptococcus agalactiae cps loci formed a single cluster that was not closely related to any of the pneumococcal cps clusters.

FIG. 1.

Cluster analysis of streptococcal polysaccharide biosynthetic loci. The relatedness of the loci was determined from the extent of sharing of HGs, adjusted for the percentage DNA sequence similarity between the genes encoding the shared HGs, as described in Materials and Methods. Clusters are defined by the dotted line at a distance of 0.3, and subclusters are defined by the dotted line at 0.05. Serotypes of S. pneumoniae (and S. agalactiae) or species of viridans group streptococci are shown at the end of each branch of the tree.

FIG. 2.

Comparisons of those cps loci within cluster 1 assigned to the same subcluster. The relatedness of the cps loci in the subcluster is from Fig. 1. The cps loci and ACT comparisons based on the amino acid sequence similarities of the products of the cps loci are shown, along with the CPS repeat unit structures, where known. CPS structures are represented as in the report by Bentley et al. (5), with the initial sugar that is attached to the lipid carrier (///) on the right. The linkage between repeat units catalyzed by the Wzy polymerase is between the two sugars marked by arrows. The genes that are predicted to catalyze the linkages in the repeat units are shown on the structure. The basis of these gene assignments is discussed in detail by Aanensen et al. (1), and uncertain GT assignments are presented in parentheses. The color keys for the functional classes of genes in the cps loci and for the sugars (and other constituents) in the CPS repeat units are shown at the bottom.

FIG. 3.

Comparisons of those cps loci within cluster 2 assigned to the same subcluster. Details are as in Fig. 2.

FIG. 3.

Comparisons of those cps loci within cluster 2 assigned to the same subcluster. Details are as in Fig. 2.

FIG. 4.

Comparisons of those cps loci within clusters 3 and 4 assigned to the same subcluster. Details are as in Fig. 2.

FIG. 5.

Comparisons of those cps loci within clusters 5 to 9 assigned to the same subcluster. Details are as in Fig. 2.