1887

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 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.

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2016-10-01
2024-03-28
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References

  1. Altschul S. F., Madden T. L., Schäffer A. A., Zhang J., Zhang Z., Miller W., Lipman D. J. 1997; Gapped blast and PSI-blast: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402 [View Article][PubMed]
    [Google Scholar]
  2. Bentley S. D., Aanensen D. M., Mavroidi A., Saunders D., Rabbinowitsch E., Collins M., Donohoe K., Harris D., Murphy L. et al. 2006; Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genet 2:e31 [View Article][PubMed]
    [Google Scholar]
  3. Brueggemann A. B., Griffiths D. T., Meats E., Peto T., Crook D. W., Spratt B. G. 2003; Clonal relationships between invasive and carriage Streptococcus pneumoniae and serotype- and clone-specific differences in invasive disease potential. J Infect Dis 187:1424–1432 [View Article][PubMed]
    [Google Scholar]
  4. Brueggemann A. B., Pai R., Crook D. W., Beall B. 2007; Vaccine escape recombinants emerge after pneumococcal vaccination in the United States. PLoS Pathog 3:e168 [View Article][PubMed]
    [Google Scholar]
  5. Burton R. L., Geno K. A., Saad J. S., Nahm M. H. 2016; Pneumococcus with the ‘6E’ cps locus produces serotype 6B capsular polysaccharide. J Clin Microbiol 54:967–971 [View Article][PubMed]
    [Google Scholar]
  6. Calix J. J., Nahm M. H. 2010; A new pneumococcal serotype, 11E, has a variably inactivated wcjE gene. J Infect Dis 202:29–38 [View Article][PubMed]
    [Google Scholar]
  7. Calix J. J., Porambo R. J., Brady A. M., Larson T. R., Yother J., Abeygunwardana C., Nahm M. H. 2012; Biochemical, genetic, and serological characterization of two capsule subtypes among Streptococcus pneumoniae serotype 20 strains: discovery of a new pneumococcal serotype. J Biol Chem 287:27885–27894 [View Article][PubMed]
    [Google Scholar]
  8. Chewapreecha C., Harris S. R., Croucher N. J., Turner C., Marttinen P., Cheng L., Pessia A., Aanensen D. M., Mather A. E. et al. 2014; Dense genomic sampling identifies highways of pneumococcal recombination. Nat Genet 46:305–309 [View Article][PubMed]
    [Google Scholar]
  9. Cornick J. E., Chaguza C., Harris S. R., Yalcin F., Senghore M., Kiran A. M., Govindpershad S., Ousmane S., Plessis M. D., Pluschke G. 2015; Region-specific diversification of the highly virulent serotype 1 Streptococcus pneumoniae . Microbial Genomics 1:1–13
    [Google Scholar]
  10. Croucher N. J., Harris S. R., Fraser C., Quail M. A., Burton J., van der Linden M., McGee L., von Gottberg A., Song J. H. et al. 2011; Rapid pneumococcal evolution in response to clinical interventions. Science 331:430–434 [View Article][PubMed]
    [Google Scholar]
  11. Croucher N. J., Finkelstein J. A., Pelton S. I., Mitchell P. K., Lee G. M., Parkhill J., Bentley S. D., Hanage W. P., Lipsitch M. 2013a; Population genomics of post-vaccine changes in pneumococcal epidemiology. Nature Genetics 45:656–663 [View Article]
    [Google Scholar]
  12. Croucher N. J., Mitchell A. M., Gould K. A., Inverarity D., Barquist L., Feltwell T., Fookes M. C., Harris S. R., Dordel J. et al. 2013b; Dominant role of nucleotide substitution in the diversification of serotype 3 pneumococci over decades and during a single infection. PLoS Genetics 9:e1003868 [View Article]
    [Google Scholar]
  13. Didelot X., Wilson D. J. 2015; ClonalFrameML: efficient inference of recombination in whole bacterial genomes. PLoS Comput Biol 11:e1004041 [View Article][PubMed]
    [Google Scholar]
  14. Ding F., Tang P., Hsu M. H., Cui P., Hu S., Yu J., Chiu C. H. 2009; Genome evolution driven by host adaptations results in a more virulent and antimicrobial-resistant Streptococcus pneumoniae serotype 14. BMC Genomics 10:158 [View Article][PubMed]
    [Google Scholar]
  15. Dunne E. M., Tikkanen L., Balloch A., Gould K., Yoannes M., Phuanukoonnon S., Licciardi P. V., Russell F. M., Mulholland E. K. et al. 2015; Characterization of 19A-like 19F pneumococcal isolates from Papua new Guinea and Fiji. New Microbes New Infect 7:86–88 [View Article][PubMed]
    [Google Scholar]
  16. Edgar R. C. 2004; muscle: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797 [View Article][PubMed]
    [Google Scholar]
  17. Feikin D. R., Kagucia E. W., Loo J. D., Link-Gelles R., Puhan M. A., Cherian T., Levine O. S., Whitney C. G., O'Brien K. L., Moore M. R. 2013; Serotype-specific changes in invasive pneumococcal disease after pneumococcal conjugate vaccine introduction: a pooled analysis of multiple surveillance sites. PLoS Med 10:e1001517 [View Article][PubMed]
    [Google Scholar]
  18. Francisco A. P., Vaz C., Monteiro P. T., Melo-Cristino J., Ramirez M., Carriço J. A. 2012; PHYLOViZ: phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 13:87 [View Article][PubMed]
    [Google Scholar]
  19. Gladstone R. A., Jefferies J. M., Tocheva A. S., Beard K. R., Garley D., Chong W. W., Bentley S. D., Faust S. N., Clarke S. C. 2015; Five winters of pneumococcal serotype replacement in UK carriage following PCV introduction. Vaccine 33:2015–2021 [View Article][PubMed]
    [Google Scholar]
  20. Hausdorff W. P., Hoet B., Adegbola R. A. 2015; Predicting the impact of new pneumococcal conjugate vaccines: serotype composition is not enough. Expert Rev Vaccines 14:413–428 [View Article][PubMed]
    [Google Scholar]
  21. Jolley K. A., Maiden M. C. 2010; BIGSdb: scalable analysis of bacterial genome variation at the population level. BMC Bioinformatics 11: [View Article][PubMed]
    [Google Scholar]
  22. Jolley K. A., Bliss C. M., Bennett J. S., Bratcher H. B., Brehony C., Colles F. M., Wimalarathna H., Harrison O. B., Sheppard S. K. et al. 2012; Ribosomal multilocus sequence typing: universal characterization of bacteria from domain to strain. Microbiology 158:1005–1015 [View Article][PubMed]
    [Google Scholar]
  23. Kolkman M. A., van der Zeijst B. A., Nuijten P. J. 1997; Functional analysis of glycosyltransferases encoded by the capsular polysaccharide biosynthesis locus of Streptococcus pneumoniae serotype 14. J Biol Chem 272:19502–19508 [View Article][PubMed]
    [Google Scholar]
  24. Letunic I., Bork P. 2011; Interactive Tree Of Life v2: online annotation and display of phylogenetic trees made easy. Nucleic Acids Res 39:W475–478 [View Article][PubMed]
    [Google Scholar]
  25. Li W., Godzik A. 2006; Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 22:1658–1659 [View Article][PubMed]
    [Google Scholar]
  26. Mavroidi A., Godoy D., Aanensen D. M., Robinson D. A., Hollingshead S. K., Spratt B. G. 2004; Evolutionary genetics of the capsular locus of serogroup 6 pneumococci. J Bacteriol 186:8181–8192 [View Article][PubMed]
    [Google Scholar]
  27. McGee L., McDougal L., Zhou J., Spratt B. G., Tenover F. C., George R., Hakenbeck R., Hryniewicz W., Lefévre J. C. et al. 2001; Nomenclature of major antimicrobial-resistant clones of Streptococcus pneumoniae defined by the pneumococcal molecular epidemiology network. J Clin Microbiol 39:2565–2571 [View Article][PubMed]
    [Google Scholar]
  28. Menezes A. P., Reis J. N., Ternes Y. M., Andrade A. L., Pimenta F. C., Carvalho M. G., Beall B. 2013; Update of pneumococcal PCR serotyping assay for detection of a commonly occurring type 19F wzy variant in Brazil. J Clin Microbiol 51:2470–2471 [View Article][PubMed]
    [Google Scholar]
  29. O'Brien K. L., Wolfson L. J., Watt J. P., Henkle E., Deloria-Knoll M., McCall N., Lee E., Mulholland K., Levine O. S. et al. 2009; Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: global estimates. Lancet 374:893–902 [View Article][PubMed]
    [Google Scholar]
  30. Page A. J., Cummins C. A., Hunt M., Wong V. K., Reuter S., Holden M. T., Fookes M., Falush D., Keane J. A., Parkhill J. 2015; Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 31:3691–3693 [View Article][PubMed]
    [Google Scholar]
  31. Pimenta F. C., Gertz R. E., Roundtree A., Yu J., Nahm M. H., McDonald R. R., Carvalho M. G., Beall B. W. 2009; Rarely occurring 19A-like cps locus from a serotype 19F pneumococcal isolate indicates continued need of serology-based quality control for PCR-based serotype determinations. J Clin Microbiol 47:2353–2354 [View Article][PubMed]
    [Google Scholar]
  32. Price M. N., Dehal P. S., Arkin A. P. 2010; FastTree 2–approximately maximum-likelihood trees for large alignments. PLoS One 5:e9490 [View Article][PubMed]
    [Google Scholar]
  33. Satzke C., Dunne E. M., Porter B. D., Klugman K. P., Mulholland E. K. PneuCarriage project group 2015; The PneuCarriage project: a multi-centre comparative study to identify the best serotyping methods for examining pneumococcal carriage in vaccine evaluation studies. PLoS Med 12:e1001903 [View Article][PubMed]
    [Google Scholar]
  34. Seemann T. 2014; Prokka: rapid prokaryotic genome annotation. Bioinformatics 30:2068–2069 [View Article][PubMed]
    [Google Scholar]
  35. Sullivan M. J., Petty N. K., Beatson S. A. 2011; Easyfig: a genome comparison visualizer. Bioinformatics 27:1009–1010 [View Article][PubMed]
    [Google Scholar]
  36. Tamura K., Stecher G., Peterson D., Filipski A., Kumar S. 2013; mega6: molecular evolutionary genetics analysis version 6.0. Mol Biol Evol 30:2725–2729 [View Article][PubMed]
    [Google Scholar]
  37. van Selm S., van Cann L. M., Kolkman M. A., van der Zeijst B. A., van Putten J. P. 2003; Genetic basis for the structural difference between Streptococcus pneumoniae serotype 15B and 15C capsular polysaccharides. Infect Immun 71:6192–6198 [View Article][PubMed]
    [Google Scholar]
  38. van Tonder A. J., Mistry S., Bray J. E., Hill D. M., Cody A. J., Farmer C. L., Klugman K. P., von Gottberg A., Bentley S. D. et al. 2014; Defining the estimated core genome of bacterial populations using a bayesian decision model. PLoS Comput Biol 10:e1003788 [View Article][PubMed]
    [Google Scholar]
  39. van Tonder A. J., Bray J. E., Roalfe L., White R., Zancolli M., Quirk S. J., Haraldsson G., Jolley K. A., Maiden M. C. et al. 2015; Genomics reveals the worldwide distribution of multidrug-resistant serotype 6e pneumococci. J Clin Microbiol 53:2271–2285 [View Article][PubMed]
    [Google Scholar]
  40. Weinberger D. M., Malley R., Lipsitch M. 2011; Serotype replacement in disease after pneumococcal vaccination. Lancet 378:1962–1973 [View Article][PubMed]
    [Google Scholar]
  41. WHO 2012; Pneumococcal vaccines WHO position paper - 2012 - recommendations. Vaccine 30:4717–4718 [View Article][PubMed]
    [Google Scholar]
  42. Wyres K. L., Lambertsen L. M., Croucher N. J., McGee L., von Gottberg A., Linares J., Jacobs M. R., Kristinsson K. G., Beall B. et al. 2012; Pneumococcal capsular switching: an historical perspective. J Infect Dis 3:439–449
    [Google Scholar]
  43. Yother J. 2011; Capsules of Streptococcus pneumoniae and other bacteria: paradigms for polysaccharide biosynthesis and regulation. Annu Rev Microbiol 65:563–581 [View Article][PubMed]
    [Google Scholar]
  44. Zerbino D. R., Birney E. 2008; Velvet: algorithms for de novo short read assembly using de Bruijn graphs. Genome Res 18:821–829 [View Article][PubMed]
    [Google Scholar]
  45. van Tonder, A. J. & Brueggemann, A. B. seqSerotyper. R https://github.com/avantonder/seqSerotyper 2016
  46. van Tonder, A. J., Bray, J. E., Quirk, S. J., Haraldsson, G., Jolley, K. A., Maiden, M. C. J., Hoffmann, S., Bentley, S. D., Haraldsson, A., Erlendsdóttir, H., Kristinsson, K. G., Brueggemann, A. B. FigShare: DOI: 10.6084/m9.figshare.3839898 2016
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