Genetic and structural elucidation of capsular polysaccharides from Streptococcus pneumoniae serotype 23A and 23B, and comparison to serotype 23F. (10th October 2017)

• Record Type: Journal Article
• Authors: Ravenscroft, Neil; Omar, Aneesa; Hlozek, Jason; Edmonds-Smith, Cesarina; Follador, Rainer; Serventi, Fabio; Lipowsky, Gerd; Kuttel, Michelle M.; Cescutti, Paola; Faridmoayer, Amirreza
• Is Part Of: Carbohydrate research. Volume 450(2017)
• Page Start: 19
• Page End: 29
• Publication Date: 2017-10-10
• Subjects: Streptococcus pneumoniae -- Capsular polysaccharide -- Serotype 23A -- Serotype 23B -- NMR spectroscopy; Carbohydrates -- Periodicals; Chemistry, Organic -- Periodicals; Biochemistry -- Periodicals; Carbohydrates -- Periodicals; Chimie organique -- Périodiques; Glucides -- Périodiques; Biochemistry; Carbohydrates; Chemistry, Organic; Periodicals; Electronic journals; 507.78
• DOI: 10.1016/j.carres.2017.08.006
• Languages: English
• ISSNs: 0008-6215

Abstract

Abstract: Streptococcus pneumoniae is a globally important encapsulated human pathogen with approximately 100 different serotypes recognized. Serogroup 23 consists of serotype 23F, present in licensed vaccines, and emerging serotypes 23A and 23B. Here, we report the previously unknown structures of the pneumococcal capsular polysaccharides serotype 23A and 23B determined using genetic analysis, NMR spectroscopy, composition and linkage analysis and Smith degradation (of polysaccharide 23A). The structure of the serotype 23A capsular polysaccharide is: →4)-β-D-Glc p -(1→3)-[[α-L-Rha p -(1→2)]-[Gro-(2→P→3)]-β-D-Gal p -(1→4)]-β-L-Rha p -(1→. This structure differs from polysaccharide 23F as it features a disaccharide backbone and the di-substituted β-Gal is linked to β-Rha as a side chain. This is due to the different polymerization position catalysed by the unusually divergent repeat unit polymerase Wzy in the 23A cps biosynthesis locus. Steric crowding in 23A, confirmed by molecular models, causes the NMR signal for H-1 of the di-substituted 2, 3-β-Gal to resonate in the α-anomeric region. The structure of the serotype 23B capsular polysaccharide is the same as 23F, but without the terminal α-Rha: →4)-β-D-Glc p -(1→4)-[Gro-(2→P→3)]-β-D-Gal p -(1→4)-β-L-Rha p -(1→. The immunodominant terminal α-Rha of 23F is more sterically crowded in 23A and absent in 23B. This may explain the reported typing cross reactions for serotype 23F: slight with 23A and none with 23B. Graphical abstract: Highlights: Serotype 23A and 23B subunit structures were predicted from genome sequence analysis. The structures of the 23A and 23B polysaccharides were elucidated. The 23A polysaccharide has a disaccharide backbone and disubstituted 2, 3-β-Gal as a side chain. The 23B polysaccharide is the same as 23F but without the terminal α-Rha.