Evolution of the capsular gene locus of Streptococcus pneumoniae serogroup 6

Abstract

Streptococcus pneumoniae expressing serogroup 6 capsules frequently causes pneumococcal infections and the evolutionary origins of the serogroup 6 strains have been extensively studied. However, these studies were performed when serogroup 6 had only two known members (serotypes 6A and 6B) and before the two new members (serotypes 6C and 6D) expressing wciNβ were found. We have therefore reinvestigated the evolutionary origins of serogroup 6 by examining the profiles of the capsule gene loci and the multilocus sequence types (MLSTs) of many serogroup 6 isolates from several continents. We confirmed that there are two classes of cps locus sequences for serogroup 6 isolates. In our study, class 2 cps sequences were limited to a few serotype 6B isolates. Neighbour-joining analysis of cps sequence profiles showed a distinct clade for 6C and moderately distinct clades for class 1 6A and 6B sequences. The serotype 6D cps profile was found within the class 1 6B clade, suggesting that it was created by recombination between 6C and 6B cps loci. Interestingly, all 6C isolates also had a unique wzy allele with a 6 bp deletion. This suggests that serotype switching to 6C involves the transfer of a large (>4 kb) gene segment that includes both the wciNβ allele and the ‘short’ wzy allele. The MLST studies of serotype 6C isolates suggest that the 6C cps locus is incorporated into many different pneumococcal genomic backgrounds but that, interestingly, 6C cps may have preferentially entered strains of the same genomic backgrounds as those of serotype 6A.

Comparison of Capsular Genes of Streptococcus pneumoniae Serotype 6A, 6B, 6C, and 6D Isolates

“…In short, this study has ensured that serotypes 6C and 6D emerged by a complicated mechanism, as shown previously (4). The cps loci of serogroup 6 isolates constitute a mosaic structure originating from diverse donors.…”

“…Distinct cps loci of serotypes 6A and 6B have previously been reported to be class 2 (4, 10). Our 6X group isolates are assumed to be very similar to class 2 isolates described in previous reports (4,10). The amino acid sequences of four genes of their cps loci were very similar to each other, indicating the same origin.…”

“…Serotype 6C, which was serotyped 6A by classical Quellung reactions, has been thought to arise only by an exchange of wciN ␤ for wciN, resulting in the replacement of galactose in 6A with glucose in 6C (2,4,13). In addition, serotype 6D is thought to have arisen by the same mechanism: the substitution of wciN of 6B with wciN ␤ in 6D (2, 3, 9).…”

Biochemical, Genetic, and Serological Characterization of Two Capsule Subtypes among Streptococcus pneumoniae Serotype 20 Strains

“…Mutations in the cps locus can directly translate to changes in capsular PS biochemical structure and antigenicity. For example, serologically distinct capsule types can arise because of inactivation of cps genes (2,20,21), because of incorporation of foreign genes into the cps locus (22), or by cps enzyme point mutations that modify carbohydrate substrate identity or glycosidic linkages (23). Loss of function mutation in whaF correlates with the loss of an ␣Glc residue in the serogroup 20 PS repeat unit.…”

Multidrug-Resistant Streptococcus pneumoniae Serotype 6D Clones in South Korea

“…It has been postulated that serotypes 6C and 6D emerged by the replacement of wciN ␤ in the capsular loci of serotypes 6A and 6B, respectively (3,22). However, two recent papers reported that the serotypes 6C and 6D emerged just by the replacement of the wciN ␤ and wciP mutation (5,23). Bratcher et al (5) proposed that serotype 6C has been produced by introduction of a DNA fragment spanning the capsular polysaccharide synthesis (cps) locus irrespective of serotypes 6A and serotype 6D has resulted from a recombination between the cps loci of serotypes 6B and 6C.…”