Putative novel cps loci in a large global collection of pneumococci

Abstract

The pneumococcus produces a polysaccharide capsule, encoded by the cps locus, that provides protection against phagocytosis and determines serotype. Nearly 100 serotypes have been identified with new serotypes still being discovered, especially in previously understudied regions. Here we present an analysis of the cps loci of more than 18 000 genomes from the Global Pneumococcal Sequencing (GPS) project with the aim of identifying novel cps loci with the potential to produce previously unrecognized capsule structures. Serotypes were assigned using whole genome sequence data and 66 of the approximately 100 known serotypes were included in the final dataset. Closer examination of each serotype's sequences identified nine putative novel cps loci (9X, 11X, 16X, 18X1, 18X2, 18X3, 29X, 33X and 36X) found in ~2.6 % of the genomes. The large number and global distribution of GPS genomes provided an unprecedented opportunity to identify novel cps loci and consider their phylogenetic and geographical distribution. Nine putative novel cps loci were identified and examples of each will undergo subsequent structural and immunological analysis.

A New Pneumococcal Capsule Type, 10D, is the 100th Serotype and Has a Large cps Fragment from an Oral Streptococcus

“…S3) (24). Indeed, Cam853 was mistyped as 10A (17,20). Further, 10A will be in a future PCV (25) and may elicit antibodies cross-reacting with 39X.…”

“…Phylogenetic analysis of 10D cps suggests that 10D cps captured the wcrO 10D gene from an oral streptococcus species, which often contains pneumococcus-like cps loci and actually produces capsular PSs (28)(29)(30)(31)(32). Specifically, wcrO 10D sequence has low homology with the four S. pneumoniae wcrO genes in serotype 33C, 34, 35F, and 36 (40 to 50% amino acid identity) even though pneumococcal cps loci have been extensively studied (more than 20,000 pneumococcal isolates [17]). In contrast, wcrO 10D shows surprisingly high homology to a gene (RS00925) in the cps gene of S. mitis strain SK145.…”

“…For instance, Streptococcus thermophilus has cps-like loci (34), and E. coli has a lipopolysaccharide (LPS) synthesis locus which resembles pneumococcal cps loci (35). While a large genetic survey (involving more than 21,000 strains) in selected sites found only several pneumococcal strains with novel genetic features (17,21), surveys of additional sites, including the sites with history of extensive usage in PCVs, may reveal additional novel serotypes.…”

“…To investigate capsule diversity, capsule loci of 21,853 pneumococcal genomes were studied as a part of the Global Pneumococcal Sequencing (GPS) project (17) and a mother-infant carriage study in the Maela refugee camp, Thailand (18). The genome studies revealed that several nasopharyngeal isolates from the children of Ethiopia (19), Cambodia (20), and Thailand (21) express a novel type of cps, labeled 39X.…”

“…Their cps loci have parts of serotypes 6C and 39, separated by a gene of unknown origin, wcrO. The isolates were previously serotyped as either 39 or 10A by the Quellung and latex agglutination tests (17,(19)(20)(21). These isolates were provisionally designated as expressing serotype 39X, pending biochemical characterization, since a large genetic difference in cps may not confer a difference in the PS (22).…”