title: Putatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes.
abstract: The pneumococcus is a leading global pathogen and a key virulence factor possessed by the majority of pneumococci is an antigenic polysaccharide capsule ('serotype'), which is encoded by the capsular (cps) locus. Approximately 100 different serotypes are known, but the extent of sequence diversity within thecpsloci of individual serotypes is not well understood. Investigating serotype-specific sequence variation is crucial to the design of sequence-based serotyping methodology, understanding pneumococcal conjugate vaccine (PCV) effectiveness and the design of future PCVs. The availability of large genome datasets makes it possible to assess population-level variation among pneumococcal serotypes and in this study 5405 pneumococcal genomes were used to investigatecpslocus diversity among 49 different serotypes. Pneumococci had been recovered between 1916 and 2014 from people of all ages living in 51 countries. Serotypes were deduced bioinformatically,cpslocus sequences were extracted and variation was assessed within thecpslocus, in the context of pneumococcal genetic lineages. Overall,cpslocus sequence diversity varied markedly: low to moderate diversity was revealed among serogroups/types 1, 3, 7, 9, 11 and 22; whereas serogroups/types 6, 19, 23, 14, 15, 18, 33 and 35 displayed high diversity. Putative novel and/or hybridcpsloci were identified among all serogroups/types apart from 1, 3 and 9. This study demonstrated thatcpslocus sequence diversity varied widely between serogroups/types. Investigation of the biochemical structure of the polysaccharide capsule of major variants, particularly PCV-related serotypes and those that appear to be novel or hybrids, is warranted.
authors.affiliation: 1​Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Andries J
authors.initials: AJ
authors.lastname: van Tonder
authors.affiliation: 2​Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: James E
authors.initials: JE
authors.lastname: Bray
authors.affiliation: 3​Clinical Microbiology, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Sigríður J
authors.initials: SJ
authors.lastname: Quirk
authors.affiliation: 3​Clinical Microbiology, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Gunnsteinn
authors.initials: G
authors.lastname: Haraldsson
authors.affiliation: 2​Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Jolley
authors.affiliation: 2​Department of Zoology, University of Oxford, Oxford, United Kingdom.
authors.forename: Martin C J
authors.initials: MCJ
authors.lastname: Maiden
authors.affiliation: 4​Department of Microbiology and Infection Control, Statens Serum Institut, Copenhagen, Denmark.
authors.forename: Steen
authors.initials: S
authors.lastname: Hoffmann
authors.affiliation: 5​Pathogen Genomics, Wellcome Trust Sanger Institute, Hinxton, United Kingdom.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Bentley
authors.affiliation: 3​Clinical Microbiology, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Ásgeir
authors.initials: Á
authors.lastname: Haraldsson
authors.affiliation: 3​Clinical Microbiology, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Helga
authors.initials: H
authors.lastname: Erlendsdóttir
authors.affiliation: 3​Clinical Microbiology, University of Iceland and Landspitali University Hospital, Reykjavik, Iceland.
authors.forename: Karl G
authors.initials: KG
authors.lastname: Kristinsson
authors.affiliation: 1​Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
authors.forename: Angela B
authors.initials: AB
authors.lastname: Brueggemann
mesh_terms: D016667:Bacterial Capsules / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D011008:Pneumococcal Infections / Q000382:microbiology*; D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial / Q000235:genetics; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000235:genetics*
chemical_list: D022242:Pneumococcal Vaccines; D011135:Polysaccharides, Bacterial
keywords: molecular epidemiology; pneumococcal capsular locus; sequence-based serotyping; vaccine impact