Pneumococcal 23B molecular subtype identified using whole genome sequencing

The polysaccharide capsule is a major virulence factor of Streptococcus pneumoniae and the target of all currently licensed pneumococcal vaccines. At present, there are 92 serologically distinct pneumococcal serotypes. Structural and antigenic variation of capsular types is the result of genetic variation within the capsular polysaccharide synthesis (CPS) locus; however, genetic variation may not always result in phenotypic differences which produce novel serotypes.With the introduction of high throughput whole genome sequencing, discovery of novel genotypic variants is not unexpected and this study describes a novel variant of the serotype 23B CPS operon. This novel variant was characterized as a novel genotypic subtype (23B1) with 70%homology to the published 23B CPS sequence. High sequence variabilitywas determined in eight cps genes involved in sugar biosynthesis. However, therewas no distinction between the classic 23B serotype and 23B1 serologically or in terms of polysaccharide structure. Phylogenetic and eBURST analysis revealed adistinct lineage for23B1withmultiple clones (UK, Thailand, andUSA) that arose at different pointsduring pneumococcal evolution. Analysis of the UK S. pneumoniae isolates (n=121) revealed an upsurge of 23B1 ST2372 in 2011, after whichthispreviouslyunseenST increasedtoreach50%proportionof the23Bsequencedisolates from2013andremainedprevalent within our sequenced isolates from later years. Therefore, although the 23B1 variant appears to have no phenotypic impact and cannot be considered as novel serotype, it appears to have led to a genetic restructuring of the UK serotype 23B population.