1887

Abstract

The pneumococcus produces a polysaccharide capsule, encoded by the 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 loci of more than 18  000 genomes from the Global Pneumococcal Sequencing (GPS) project with the aim of identifying novel 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 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 loci and consider their phylogenetic and geographical distribution. Nine putative novel loci were identified and examples of each will undergo subsequent structural and immunological analysis.

  • This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000274
2019-06-11
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/mgen/5/7/mgen000274.html?itemId=/content/journal/mgen/10.1099/mgen.0.000274&mimeType=html&fmt=ahah

References

  1. Wahl B, O'Brien KL, Greenbaum A, Majumder A, Liu L et al. Burden of Streptococcus pneumoniae and Haemophilus influenzae type B disease in children in the era of conjugate vaccines: global, regional, and national estimates for 2000-15. Lancet Glob Health 2018; 6:e744–e757 [View Article]
    [Google Scholar]
  2. Briles DE, Crain MJ, Gray BM, Forman C, Yother J. Strong association between capsular type and virulence for mice among human isolates of Streptococcus pneumoniae . Infect Immun 1992; 60:111–116
    [Google Scholar]
  3. Hyams C, Camberlein E, Cohen JM, Bax K, Brown JS. The Streptococcus pneumoniae capsule inhibits complement activity and neutrophil phagocytosis by multiple mechanisms. Infect Immun 2010; 78:704–715 [View Article]
    [Google Scholar]
  4. Larson TR, Yother J. Streptococcus pneumoniae capsular polysaccharide is linked to peptidoglycan via a direct glycosidic bond to beta-D-N-acetylglucosamine. Proc Natl Acad Sci U S A 2017; 114:5695–5700 [View Article]
    [Google Scholar]
  5. Bentley SD, Aanensen DM, Mavroidi A, Saunders D, Rabbinowitsch E et al. Genetic analysis of the capsular biosynthetic locus from all 90 pneumococcal serotypes. PLoS Genet 2006; 2:e31 [View Article]
    [Google Scholar]
  6. Calix JJ, Nahm MH. A new pneumococcal serotype, 11E, has a variably inactivated wcjE gene. J Infect Dis 2010; 202:29–38 [View Article]
    [Google Scholar]
  7. Geno KA, Saad JS, Nahm MH. Discovery of novel pneumococcal serotype 35D, a natural WciG-Deficient variant of serotype 35B. J Clin Microbiol 2017; 55:1416–1425 [View Article]
    [Google Scholar]
  8. Mostowy RJ, Croucher NJ, De Maio N, Chewapreecha C, Salter SJ et al. Pneumococcal capsule synthesis locus CPS as evolutionary hotspot with potential to generate novel serotypes by recombination. Mol Biol Evol 2017; 34:2537–2554 [View Article]
    [Google Scholar]
  9. Yother J. Capsules of Streptococcus pneumoniae and other bacteria: paradigms for polysaccharide biosynthesis and regulation. Annu Rev Microbiol 2011; 65:563–581 [View Article]
    [Google Scholar]
  10. Geno KA, Gilbert GL, Song JY, Skovsted IC, Klugman KP et al. Pneumococcal capsules and their types: past, present, and future. Clin Microbiol Rev 2015; 28:871–899 [View Article]
    [Google Scholar]
  11. Aanensen DM, Mavroidi A, Bentley SD, Reeves PR, Spratt BG. Predicted functions and linkage specificities of the products of the Streptococcus pneumoniae capsular biosynthetic loci. J Bacteriol 2007; 189:7856–7876 [View Article]
    [Google Scholar]
  12. Mavroidi A, Aanensen DM, Godoy D, Skovsted IC, Kaltoft MS et al. Genetic relatedness of the Streptococcus pneumoniae capsular biosynthetic loci. J Bacteriol 2007; 189:7841–7855 [View Article]
    [Google Scholar]
  13. Ladhani SN, Collins S, Djennad A, Sheppard CL, Borrow R et al. Rapid increase in non-vaccine serotypes causing invasive pneumococcal disease in England and Wales, 2000-17: a prospective national observational cohort study. Lancet Infect Dis 2018; 18:441–451 [View Article]
    [Google Scholar]
  14. Ben-Shimol S, Givon-Lavi N, Grisaru-Soen G, Megged O, Greenberg D et al. Comparative incidence dynamics and serotypes of meningitis, bacteremic pneumonia and other-IPD in young children in the PCV era: insights from Israeli surveillance studies. Vaccine 2018; 36:5477–5484 [View Article]
    [Google Scholar]
  15. Savulescu C, Krizova P, Lepoutre A, Mereckiene J, Vestrheim DF et al. Effect of high-valency pneumococcal conjugate vaccines on invasive pneumococcal disease in children in SpIDnet countries: an observational multicentre study. Lancet Respir Med 2017; 5:648–656 [View Article]
    [Google Scholar]
  16. Croucher NJ, Finkelstein JA, Pelton SI, Mitchell PK, Lee GM et al. Population genomics of post-vaccine changes in pneumococcal epidemiology. Nat Genet 2013; 45:656–663 [View Article]
    [Google Scholar]
  17. Gladstone RA, Devine V, Jones J, Cleary D, Jefferies JM et al. Pre-vaccine serotype composition within a lineage signposts its serotype replacement - a carriage study over 7 years following pneumococcal conjugate vaccine use in the UK. Microb Genom 2017; 3:e000119 [View Article]
    [Google Scholar]
  18. Salter SJ, Hinds J, Gould KA, Lambertsen L, Hanage WP et al. Variation at the capsule locus, CPS, of mistyped and non-typable Streptococcus pneumoniae isolates. Microbiology 2012; 158:1560–1569 [View Article]
    [Google Scholar]
  19. van Tonder AJ, Bray JE, Quirk SJ, Haraldsson G, Jolley KA et al. Putatively novel serotypes and the potential for reduced vaccine effectiveness: capsular locus diversity revealed among 5405 pneumococcal genomes. Microb Genom 2016; 2:000090 [View Article]
    [Google Scholar]
  20. SW L, Gladstone RA, van Tonder AJ, Hawkins PA, Kwambana-Adams B et al. Global distribution of invasive serotype 35D Streptococcus pneumoniae isolates following introduction of 13-Valent pneumococcal conjugate vaccine. J Clin Microbiol 2018; 56:
    [Google Scholar]
  21. Epping L, van Tonder AJ, Gladstone RA, Bentley SD et al. SeroBA: rapid high-throughput serotyping of Streptococcus pneumoniae from whole genome sequence data. Microb Genom 2018
    [Google Scholar]
  22. Hilty M, Wüthrich D, Salter SJ, Engel H, Campbell S et al. Global phylogenomic analysis of nonencapsulated Streptococcus pneumoniae reveals a deep-branching classic lineage that is distinct from multiple sporadic lineages. Genome Biol Evol 2014; 6:3281–3294 [View Article]
    [Google Scholar]
  23. Park IH, Kim KH, Andrade AL, Briles DE, McDaniel LS et al. Nontypeable pneumococci can be divided into multiple CPS types, including one type expressing the novel gene pspK. MBio 2012; 3: [View Article]
    [Google Scholar]
  24. Gladstone RA, Lo SW, Lees JA, Croucher NJ, van Tonder AJ et al. International genomic definition of pneumococcal lineages, to contextualise disease, antibiotic resistance and vaccine impact. EBioMedicine 2019; 43:338–346
    [Google Scholar]
  25. Lees JA, Harris SR, Tonkin-Hill G, Gladstone RA, Lo SW et al. Fast and flexible bacterial genomic epidemiology with PopPUNK. Genome Res 2019; 29:304–316 [View Article]
    [Google Scholar]
  26. Li H, Handsaker B, Wysoker A, Fennell T, Ruan J et al. The sequence Alignment/Map format and SAMtools. Bioinformatics 2009; 25:2078–2079 [View Article]
    [Google Scholar]
  27. Harris SR, Feil EJ, Holden MTG, Quail MA, Nickerson EK et al. Evolution of MRSA during hospital transmission and intercontinental spread. Science 2010; 327:469–474 [View Article]
    [Google Scholar]
  28. Page AJ, Taylor B, Delaney AJ, Soares J, Seemann T et al. SNP-sites: rapid efficient extraction of SNPs from multi-FASTA alignments. Microb Genom 2016; 2:e000056 [View Article]
    [Google Scholar]
  29. Price MN, Dehal PS, Arkin AP. FastTree 2 – approximately maximum-likelihood trees for large alignments. PLoS One 2010; 5:e9490 [View Article]
    [Google Scholar]
  30. Jain C, Rodriguez-R LM, Phillippy AM, Konstantinidis KT, Aluru S. High-throughput ani analysis of 90K prokaryotic genomes reveals clear species boundaries. bioRxiv 2017; 225342:
    [Google Scholar]
  31. Li W, Godzik A. Cd-hit: a fast program for clustering and comparing large sets of protein or nucleotide sequences. Bioinformatics 2006; 22:1658–1659 [View Article]
    [Google Scholar]
  32. Altschul SF, Madden TL, Schäffer AA, Zhang J, Zhang Z et al. Gapped blast and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 1997; 25:3389–3402 [View Article]
    [Google Scholar]
  33. Carver TJ, Rutherford KM, Berriman M, Rajandream M-A, Barrell BG et al. Act: Produces Serotype 6B Capsular polysaccharide. Bioinformatics 2005; 21:3422–3423 [View Article]
    [Google Scholar]
  34. Burton RL, Geno KA, Saad JS, Nahm MH. Pneumococca 23B molecular subtype identified using whole genome sequencing. J Clin Microbiol 2016; 54:967–971 [View Article]
    [Google Scholar]
  35. Kapatai G, Sheppard CL, Troxler LJ, Litt DJ, Furrer J et al. Pneumococcal 23B molecular subtype identified using whole genome sequencing. Genome Biol Evol 2017; 9:2145–2158 [View Article]
    [Google Scholar]
  36. Xayarath B, Yother J. Mutations blocking side chain assembly, polymerization, or transport of a Wzy-dependent Streptococcus pneumoniae capsule are lethal in the absence of suppressor mutations and can affect polymer transfer to the cell wall. J Bacteriol 2007; 189:3369–3381 [View Article]
    [Google Scholar]
  37. Bush CA, Yang J, Yu B, Cisar JO. Chemical structures of Streptococcus pneumoniae capsular polysaccharide type 39 (CPS39), CPS47F, and CPS34 characterized by nuclear magnetic resonance spectroscopy and their relation to CPS10A. J Bacteriol 2014; 196:3271–3278 [View Article]
    [Google Scholar]
  38. Manna S, Dunne EM, Ortika BD, Pell CL, Kama M et al. Discovery of a Streptococcus pneumoniae serotype 33F capsular polysaccharide locus that lacks wcjE and contains a wcyO pseudogene. PLoS One 2018; 13:e0206622 [View Article]
    [Google Scholar]
  39. Oliver MB, Jones C, Larson TR, Calix JJ, Zartler ER et al. Streptococcus pneumoniae serotype 11D has a bispecific glycosyltransferase and expresses two different capsular polysaccharide repeating units. J Biol Chem 2013; 288:21945–21954 [View Article]
    [Google Scholar]
  40. Manna S, Ortika BD, Dunne EM, Holt KE, Kama M et al. A novel genetic variant of Streptococcus pneumoniae serotype 11A discovered in Fiji. Clin Microbiol Infect 2018; 24:428.e1–428.e7 [View Article]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000274
Loading
/content/journal/mgen/10.1099/mgen.0.000274
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Supplementary material 1

EXCEL

Supplementary material 1

PDF
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error