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dc.contributor.authorvan Tonder, Andriesen
dc.contributor.authorBray, James Een
dc.contributor.authorQuirk, Sigríður Jen
dc.contributor.authorHaraldsson, Gunnsteinnen
dc.contributor.authorJolley, Keith Aen
dc.contributor.authorMaiden, Martin CJen
dc.contributor.authorHoffmann, Steenen
dc.contributor.authorBentley, Stephen Den
dc.contributor.authorHaraldsson, Ásgeiren
dc.contributor.authorErlendsdóttir, Helgaen
dc.contributor.authorKristinsson, Karl Gen
dc.contributor.authorBrueggemann, Angela Ben
dc.description.abstractThe 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 the cps loci 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 investigate cps locus 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, cps locus sequences were extracted and variation was assessed within the cps locus, in the context of pneumococcal genetic lineages. Overall, cps locus 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 hybrid cps loci were identified among all serogroups/types apart from 1, 3 and 9. This study demonstrated that cps locus 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.
dc.description.sponsorshipThis work was supported by a Wellcome Trust Biomedical Research Fund award (04992/Z/14/Z) to M. J. C. M., K. A. J., and A. B. B.; a Wellcome Trust career development fellowship (083511/Z/07/Z) to A. B. B; and a University of Oxford John Fell Fund award (123/734) to A. B. B. Core funding for the Sanger Institute was provided by the Wellcome Trust (098051). Funding for the Icelandic vaccine impact study was provided by GlaxoSmithKline Biologicals SA and the Landspítali University Hospital Research Fund to K. G. K., A. H., H. E., S. D. B., and A. B. B.
dc.rightsAttribution 4.0 International
dc.subjectmolecular epidemiologyen
dc.subjectpneumococcal capsular locusen
dc.subjectsequence-based serotypingen
dc.subjectvaccine impacten
dc.subjectBacterial Capsulesen
dc.subjectGenetic Variationen
dc.subjectPneumococcal Infectionsen
dc.subjectPneumococcal Vaccinesen
dc.subjectPolysaccharides, Bacterialen
dc.subjectStreptococcus pneumoniaeen
dc.titlePutatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes.en
prism.publicationNameMicrobial Genomicsen
dc.contributor.orcidvan Tonder, Andries [0000-0002-4380-5250]
rioxxterms.typeJournal Article/Reviewen

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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International