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Microbial Genomics logo Microbial Genomics

Volume 6, Issue 9

Diversification in immunogenicity genes caused by selective pressures in invasive meningococci Open Access

Abstract

We studied population genomics of 486 isolates causing meningitis in the Netherlands during the period 1979–2003 and 2006–2013 using whole-genome sequencing to evaluate the impact of a hyperendemic period of serogroup B invasive disease. The majority of serogroup B isolates belonged to ST-41/44 (41 %) and ST-32 complex (16 %). Comparing the time periods, before and after the decline of serogroup B invasive disease, there was a decrease of ST-41/44 complex sequences (=0.002). We observed the expansion of a sub-lineage within ST-41/44 complex sequences being associated with isolation from the 1979–2003 time period (=0.014). Isolates belonging to this sub-lineage expansion within ST-41/44 complex were marked by four antigen allele variants. Presence of these allele variants was associated with isolation from the 1979–2003 time period after correction for multiple testing (Wald test, =0.0043 for FetA 1–5; =0.0035 for FHbp 14; =0.012 for PorA 7–2.4 and =0.0031 for NHBA two peptide allele). These sequences were associated with 4CMenB vaccine coverage (Fisher’s exact test, <0.001). Outside of the sub-lineage expansion, isolates with markedly lower levels of predicted vaccine coverage clustered in phylogenetic groups showing a trend towards isolation in the 2006–2013 time period (=0.08). In conclusion, we show the emergence and decline of a sub-lineage expansion within ST-41/44 complex isolates concurrent with a hyperendemic period in meningococcal meningitis. The expansion was marked by specific antigen peptide allele combinations. We observed preliminary evidence for decreasing 4CMenB vaccine coverage in the post-hyperendemic period.

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Keyword(s): 4CMenB , antigens , evolution , genome sequencing and Neisseria meningitidis
Funding
This study was supported by the:
  • Rijksinstituut voor Volksgezondheid en Milieu
    • Principal Award Recipient: Arie van der Ende
  • Medical Research Foundation (Award 1365620)
    • Principal Award Recipient: John A Lees
  • Wellcome Trust (Award 098051)
    • Principal Award Recipient: Stephen D Bentley
  • ZonMw (Award 016.116.358)
    • Principal Award Recipient: Diederik van de Beek
  • H2020 European Research Council (Award 281156)
    • Principal Award Recipient: Diederik van de Beek
© 2020 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2020-08-10
2026-01-15

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References

  1. van de Beek D, Brouwer MC, Hasbun R, Koedel U, Whitney CG et al. Community-acquired bacterial meningitis. Nat Rev Dis Prim 2016; 3:16074
     [Google Scholar]
  2. Bijlsma MW, Bekker V, Brouwer MC, Spanjaard L, van de Beek D et al. Epidemiology of invasive meningococcal disease in the Netherlands, 1960–2012: an analysis of national surveillance data. Lancet Infect Dis 2014; 14:805–812 [View Article]
     [Google Scholar]
  3. Buckee CO, Jolley KA, Recker M, Penman B, Kriz P et al. Role of selection in the emergence of lineages and the evolution of virulence in Neisseria meningitidis . Proc Natl Acad Sci U S A 2008; 105:15082–15087 [View Article]
     [Google Scholar]
  4. Stollenwerk N, Maiden MCJ, Jansen VAA. Diversity in pathogenicity can cause outbreaks of meningococcal disease. Proc Natl Acad Sci U S A 2004; 101:10229–10234 [View Article]
     [Google Scholar]
  5. Urwin R, Russell JE, Thompson EAL, Holmes EC, Feavers IM et al. Distribution of surface protein variants among hyperinvasive meningococci: implications for vaccine design. Infect Immun 2004; 72:5955–5962 [View Article]
     [Google Scholar]
  6. Buckee CO, Gupta S, Kriz P, Maiden MCJ, Jolley KA. Long-Term evolution of antigen repertoires among carried meningococci. Proc R Soc B 2010; 277:1635–1641 [View Article]
     [Google Scholar]
  7. Bambini S, Piet J, Muzzi A, Keijzers W, Comandi S et al. An analysis of the sequence variability of meningococcal fHbp, NadA and NHBA over a 50-year period in the Netherlands. PLoS One 2013; 8:e65043 [View Article]
     [Google Scholar]
  8. Brehony C, Wilson DJ, Maiden MCJ. Variation of the factor H-binding protein of Neisseria meningitidis . Microbiology 2009; 155:4155–4169 [View Article]
     [Google Scholar]
  9. van de Waterbeemd B, Zomer G, Kaaijk P, Ruiterkamp N, Wijffels RH et al. Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis . PLoS One 2013; 8:e65157 [View Article]
     [Google Scholar]
  10. Marsay L, Dold C, Green CA, Rollier CS, Norheim G et al. A novel meningococcal outer membrane vesicle vaccine with constitutive expression of FetA: a phase I clinical trial. J Infect 2015; 71:326–337 [View Article]
     [Google Scholar]
  11. Koeberling O, Welsch JA, Granoff DM. Improved immunogenicity of a H44/76 group B outer membrane vesicle vaccine with over-expressed genome-derived Neisserial antigen 1870. Vaccine 2007; 25:1912–1920 [View Article]
     [Google Scholar]
  12. Donnelly J, Medini D, Boccadifuoco G, Biolchi A, Ward J et al. Qualitative and quantitative assessment of meningococcal antigens to evaluate the potential strain coverage of protein-based vaccines. Proc Natl Acad Sci U S A 2010; 107:19490–19495 [View Article]
     [Google Scholar]
  13. de Gans J, van de Beek D. Dexamethasone in adults with bacterial meningitis. N Engl J Med 2002; 347:1549–1556 [View Article]
     [Google Scholar]
  14. van de Beek D, de Gans J, Spanjaard L, Weisfelt M, Reitsma JB et al. Clinical features and prognostic factors in adults with bacterial meningitis. N Engl J Med Overseas Ed 2004; 351:1849–1859 [View Article]
     [Google Scholar]
  15. Bijlsma MW, Brouwer MC, Kasanmoentalib ES, Kloek AT, Lucas MJ et al. Community-acquired bacterial meningitis in adults in the Netherlands, 2006–14: a prospective cohort study. Lancet Infect Dis 2016; 16:339–347 [View Article]
     [Google Scholar]
  16. Lees JA, Kremer PHC, Manso AS, Croucher NJ, Ferwerda B et al. Large scale genomic analysis shows no evidence for pathogen adaptation between the blood and cerebrospinal fluid niches during bacterial meningitis. Microb Genomics 2017; 3:e000103 [View Article]
     [Google Scholar]
  17. Page AJ, De Silva N, Hunt M, Quail MA, Parkhill J et al. Robust high-throughput prokaryote de novo assembly and improvement pipeline for Illumina data. Microb genomics 2016; 2:e000083 [View Article]
     [Google Scholar]
  18. Seemann T. Prokka: rapid prokaryotic genome annotation. Bioinformatics 2014; 30:2068–2069 [View Article]
     [Google Scholar]
  19. Page AJ, Cummins CA, Hunt M, Wong VK, Reuter S et al. Roary: rapid large-scale prokaryote pan genome analysis. Bioinformatics 2015; 31:3691–3693 [View Article]
     [Google Scholar]
  20. Stamatakis A. RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 2014; 30:1312–1313 [View Article]
     [Google Scholar]
  21. Argimón S, Abudahab K, Goater RJE, Fedosejev A, Bhai J et al. Microreact: visualizing and sharing data for genomic epidemiology and phylogeography. Microb Genom 2016; 2:e000093 [View Article]
     [Google Scholar]
  22. Cheng L, Connor TR, Sirén J, Aanensen DM, Corander J. Hierarchical and spatially explicit clustering of DNA sequences with BAPS software. Mol Biol Evol 2013; 30:1224–1228 [View Article]
     [Google Scholar]
  23. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15 [View Article]
     [Google Scholar]
  24. Didelot X, Croucher NJ, Bentley SD, Harris SR, Wilson DJ. Bayesian inference of ancestral dates on bacterial phylogenetic trees. Nucleic Acids Res 2018; 46:e134 [View Article]
     [Google Scholar]
  25. Nguyen L-T, Schmidt HA, von Haeseler A, Minh BQ. IQ-TREE: a fast and effective stochastic algorithm for estimating maximum-likelihood phylogenies. Mol Biol Evol 2015; 32:268–274 [View Article]
     [Google Scholar]
  26. Pond SLK, Frost SDW, Muse SV. HyPhy: hypothesis testing using phylogenies. Bioinformatics 2005; 21:676–679 [View Article]
     [Google Scholar]
  27. Muzzi A, Brozzi A, Serino L, Bodini M, Abad R et al. Genetic meningococcal antigen typing system (gMATS): a genotyping tool that predicts 4CMenB strain coverage worldwide. Vaccine 2019; 37:991–1000 [View Article]
     [Google Scholar]
  28. Vogel U, Taha M-K, Vazquez JA, Findlow J, Claus H et al. Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment. Lancet Infect Dis 2013; 13:416–425 [View Article]
     [Google Scholar]
  29. Parikh SR, Newbold L, Slater S, Stella M, Moschioni M et al. Meningococcal serogroup B strain coverage of the multicomponent 4CMenB vaccine with corresponding regional distribution and clinical characteristics in England, Wales, and Northern Ireland, 2007–08 and 2014–15: a qualitative and quantitative assessment. Lancet Infect Dis 2017; 17:754–762 [View Article]
     [Google Scholar]
  30. Rodrigues CMC, Chan H, Vipond C, Jolley K, Harrison OB et al. Typing complex meningococcal vaccines to understand diversity and population structure of key vaccine antigens. Wellcome Open Res 2018; 3:151 [View Article]
     [Google Scholar]
  31. Zhu P, van der Ende A, Falush D, Brieske N, Morelli G et al. Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis. Proc Natl Acad Sci U S A 2001; 98:5234–5239 [View Article]
     [Google Scholar]
  32. Gibson B, Eyre-Walker A. Investigating evolutionary rate variation in bacteria. J Mol Evol 2019; 87:317–326 [View Article]
     [Google Scholar]
  33. Green LR, Al-Rubaiawi AA, Al-Maeni MARM, Harrison OB, Blades M et al. Localized hypermutation is the major driver of meningococcal genetic variability during persistent asymptomatic carriage. mBio 2020; 11:e03068–19 [View Article]
     [Google Scholar]
  34. Lamelas A, Harris SR, Röltgen K, Dangy J-P, Hauser J et al. Emergence of a new epidemic Neisseria meningitidis serogroup a clone in the African meningitis belt: high-resolution picture of genomic changes that mediate immune evasion. mBio 2014; 5:e01974–14 [View Article]
     [Google Scholar]
  35. Pandey A, Cleary DW, Laver JR, Gorringe A, Deasy AM et al. Microevolution of Neisseria lactamica during nasopharyngeal colonisation induced by controlled human infection. Nat Commun 2018; 9:4753 [View Article]
     [Google Scholar]
  36. Vos M, Didelot X. A comparison of homologous recombination rates in bacteria and archaea. ISME J 2009; 3:199–208 [View Article]
     [Google Scholar]
  37. Vigué L, Eyre-Walker A. The comparative population genetics of Neisseria meningitidis and Neisseria gonorrhoeae . PeerJ 2019; 7:e7216 [View Article]
     [Google Scholar]
  38. Kong Y, Ma JH, Warren K, Tsang RSW, Low DE et al. Homologous recombination drives both sequence diversity and gene content variation in Neisseria meningitidis . Genome Biol Evol 2013; 5:1611–1627 [View Article]
     [Google Scholar]
  39. Caugant DA, Brynildsrud OB. Neisseria meningitidis: using genomics to understand diversity, evolution and pathogenesis. Nat Rev Microbiol 2020; 18:84–96 [View Article]
     [Google Scholar]
  40. van der Ende A, Hopman CTP, Dankert J. Multiple mechanisms of phase variation of PorA in Neisseria meningitidis . Infect Immun 2000; 68:6685–6690 [View Article]
     [Google Scholar]
  41. Christensen H, May M, Bowen L, Hickman M, Trotter CL. Meningococcal carriage by age: a systematic review and meta-analysis. Lancet Infect Dis 2010; 10:853–861 [View Article]
     [Google Scholar]
  42. Thompson MJ, Ninis N, Perera R, Mayon-White R, Phillips C et al. Clinical recognition of meningococcal disease in children and adolescents. The Lancet 2006; 367:397–403 [View Article]
     [Google Scholar]
  43. Hill DMC, Lucidarme J, Gray SJ, Newbold LS, Ure R et al. Genomic epidemiology of age-associated meningococcal lineages in national surveillance: an observational cohort study. Lancet Infect Dis 2015
     [Google Scholar]
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Diversification in immunogenicity genes caused by selective pressures in invasive meningococci
M Gen 6, e000422 (2020); https://doi.org/10.1099/mgen.0.000422
/content/journal/mgen/10.1099/mgen.0.000422
/content/journal/mgen/10.1099/mgen.0.000422
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