1887

Abstract

colonizes the human oropharynx and transmits mainly via asymptomatic carriage. Actual outbreaks of meningococcal meningitis are comparatively rare and occur when susceptible populations are exposed to hypervirulent clones, genetically distinct from the main carriage isolates. However, carriage isolates can evolve into pathogens through a limited number of recombination events. The present study examines the potential for the sequence type (ST)-192, by far the dominant clone recovered in recent meningococcal carriage studies in sub-Saharan Africa, to evolve into a pathogen. We used whole-genome sequencing on a collection of 478 meningococcal isolates sampled from 1- to 29- year-old healthy individuals in Arba Minch, southern Ethiopia in 2014. The ST-192 clone was identified in nearly 60 % of the carriers. Using complementary short- and long-read techniques for whole-genome sequencing, we were able to completely resolve genomes and thereby identify genomic differences between the ST-192 carriage strain and known pathogenic clones with the highest possible resolution. We conclude that it is possible, but unlikely, that ST-192 could evolve into a significant pathogen, thus, becoming the major invasive meningococcus clone in the meningitis belt of Africa following upcoming mass vaccination with a polyvalent conjugate vaccine that targets the A, C, W, Y and X capsules.

Loading

Article metrics loading...

/content/journal/mgen/10.1099/mgen.0.000290
2019-08-01
2019-09-18
Loading full text...

Full text loading...

/deliver/fulltext/mgen/5/8/mgen000290.html?itemId=/content/journal/mgen/10.1099/mgen.0.000290&mimeType=html&fmt=ahah

References

  1. 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 [CrossRef]
    [Google Scholar]
  2. Stephens DS, Greenwood B, Brandtzaeg P. Epidemic meningitis, meningococcaemia, and Neisseria meningitidis. The Lancet 2007;369:2196–2210 [CrossRef]
    [Google Scholar]
  3. Harrison LH, Trotter CL, Ramsay ME. Global epidemiology of meningococcal disease. Vaccine 2009;27 (Suppl. 2):B51–B63 [CrossRef]
    [Google Scholar]
  4. Findlow H, Vogel U, Mueller JE, Curry A, Njanpop-Lafourcade B-M et al. Three cases of invasive meningococcal disease caused by a capsule null locus strain circulating among healthy carriers in Burkina Faso. J Infect Dis 2007;195:1071–1077 [CrossRef]
    [Google Scholar]
  5. Johswich KO, Zhou J, Law DKS, St Michael F, McCaw SE et al. Invasive potential of nonencapsulated disease isolates of Neisseria meningitidis. Infect Immun 2012;80:2346–2353 [CrossRef]
    [Google Scholar]
  6. Xu Z, Zhu B, Xu L, Gao Y, Shao Z. First case of Neisseria meningitidis capsule null locus infection in China. Infect Dis 2015;47:591–592 [CrossRef]
    [Google Scholar]
  7. Harrison OB, Claus H, Jiang Y, Bennett JS, Bratcher HB et al. Description and nomenclature of Neisseria meningitidis capsule locus. Emerg Infect Dis 2013;19:566–573 [CrossRef]
    [Google Scholar]
  8. Jafri RZ, Ali A, Messonnier NE, Tevi-Benissan C, Durrheim D et al. Global epidemiology of invasive meningococcal disease. Popul Health Metr 2013;11:17 [CrossRef]
    [Google Scholar]
  9. Yazdankhah SP, Caugant DA. Neisseria meningitidis: an overview of the carriage state. J Med Microbiol 2004;53:821–832 [CrossRef]
    [Google Scholar]
  10. Tzeng YL, Thomas J, Stephens DS. Regulation of capsule in Neisseria meningitidis. Crit Rev Microbiol 2016;42:759–772 [CrossRef]
    [Google Scholar]
  11. Claus H, Maiden MCJ, Maag R, Frosch M, Vogel U. Many carried meningococci lack the genes required for capsule synthesis and transport. Microbiology 2002;148:1813–1819 [CrossRef]
    [Google Scholar]
  12. Neri A, Fazio C, Ambrosio L, Vacca P, Barbui A et al. Carriage meningococcal isolates with capsule null locus dominate among high school students in a non-endemic period, Italy, 2012-2013. Int J Med Microbiol 2019;309:182–188 [CrossRef]
    [Google Scholar]
  13. Hoang LMN, Thomas E, Tyler S, Pollard AJ, Stephens G et al. Rapid and fatal meningococcal disease due to a strain of Neisseria meningitidis containing the capsule null locus. Clin Infect Dis 2005;40:e38–e42 [CrossRef]
    [Google Scholar]
  14. Ganesh K, Allam M, Wolter N, Bratcher HB, Harrison OB et al. Molecular characterization of invasive capsule null Neisseria meningitidis in South Africa. BMC Microbiol 2017;17:40 [CrossRef]
    [Google Scholar]
  15. Nicolas P, Djibo S, Tenebray B, Castelli P, Stor R et al. Populations of pharyngeal meningococci in Niger. Vaccine 2007;25:A53–A57 [CrossRef]
    [Google Scholar]
  16. Greenwood BM, Aseffa A, Caugant DA, Diallo K, Kristiansen PA et al. Narrative review of methods and findings of recent studies on the carriage of meningococci and other Neisseria species in the African Meningitis Belt. Trop Med Int Health 2019;24:143–154 [CrossRef]
    [Google Scholar]
  17. Bårnes GK, Kristiansen PA, Beyene D, Workalemahu B, Fissiha P et al. Prevalence and epidemiology of meningococcal carriage in southern Ethiopia prior to implementation of MenAfriVac, a conjugate vaccine. BMC Infect Dis 2016;16:639 [CrossRef]
    [Google Scholar]
  18. Spinosa MR, Progida C, Talà A, Cogli L, Alifano P et al. The Neisseria meningitidis capsule is important for intracellular survival in human cells. Infect Immun 2007;75:3594–3603 [CrossRef]
    [Google Scholar]
  19. Brynildsrud OB, Eldholm V, Bohlin J, Uadiale K, Obaro S et al. Acquisition of virulence genes by a carrier strain gave rise to the ongoing epidemics of meningococcal disease in West Africa. Proc Natl Acad Sci USA 2018;115:5510–5515 [CrossRef]
    [Google Scholar]
  20. Chen WH, Neuzil KM, Boyce CR, Pasetti MF, Reymann MK et al. Safety and immunogenicity of a pentavalent meningococcal conjugate vaccine containing serogroups A, C, Y, W, and X in healthy adults: a phase 1, single-centre, double-blind, randomised, controlled study. Lancet Infect Dis 2018;18:1088–1096 [CrossRef]
    [Google Scholar]
  21. Bårnes GK, Brynildsrud OB, Børud B, Workalemahu B, Kristiansen PA et al. Whole genome sequencing reveals within-host genetic changes in paired meningococcal carriage isolates from Ethiopia. BMC Genomics 2017;18:407 [CrossRef]
    [Google Scholar]
  22. Bolger AM, Lohse M, Usadel B. Trimmomatic: a flexible trimmer for Illumina sequence data. Bioinformatics 2014;30:2114–2120 [CrossRef]
    [Google Scholar]
  23. Bankevich A, Nurk S, Antipov D, Gurevich AA, Dvorkin M et al. SPAdes: a new genome assembly algorithm and its applications to single-cell sequencing. J Comput Biol 2012;19:455–477 [CrossRef]
    [Google Scholar]
  24. Wood DE, Salzberg SL. Kraken: ultrafast metagenomic sequence classification using exact alignments. Genome Biol 2014;15:R46 [CrossRef]
    [Google Scholar]
  25. Wick RR, Judd LM, Gorrie CL, Holt KE. Unicycler: resolving bacterial genome assemblies from short and long sequencing reads. PLoS Comput Biol 2017;13:e1005595 [CrossRef]
    [Google Scholar]
  26. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014;15:524 [CrossRef]
    [Google Scholar]
  27. 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 [CrossRef]
    [Google Scholar]
  28. Nguyen LT, 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 [CrossRef]
    [Google Scholar]
  29. Hoang DT, Chernomor O, von Haeseler A, Minh BQ, Vinh LS. UFBoot2: improving the ultrafast bootstrap approximation. Mol Biol Evol 2018;35:518–522 [CrossRef]
    [Google Scholar]
  30. Bouckaert RR, Drummond AJ. bModelTest: Bayesian phylogenetic site model averaging and model comparison. BMC Evol Biol 2017;17:42 [CrossRef]
    [Google Scholar]
  31. Hadfield J, Croucher NJ, Goater RJ, Abudahab K, Aanensen DM et al. Phandango: an interactive viewer for bacterial population genomics. Bioinformatics 2018;34:292–293 [CrossRef]
    [Google Scholar]
  32. Maiden MCJ, Harrison OB. Population and functional genomics of Neisseria revealed with gene-by-gene approaches. J Clin Microbiol 2016;54:1949–1955 [CrossRef]
    [Google Scholar]
  33. Eren AM, Esen Özcan C, Quince C, Vineis JH, Morrison HG et al. Anvi'o: an advanced analysis and visualization platform for 'omics data. PeerJ 2015;3:e1319 [CrossRef]
    [Google Scholar]
  34. Jolley KA, Bliss CM, Bennett JS, Bratcher HB, Brehony C et al. Ribosomal multilocus sequence typing: universal characterization of bacteria from domain to strain. Microbiology 2012;158:1005–1015 [CrossRef]
    [Google Scholar]
  35. Linhartová I, Bumba L, Mašín J, Basler M, Osička R et al. Rtx proteins: a highly diverse family secreted by a common mechanism. FEMS Microbiol Rev 2010;34:1076–1112 [CrossRef]
    [Google Scholar]
  36. Hammerschmidt S, Hilse R, van Putten JP, Gerardy-Schahn R, Unkmeir A et al. Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. Embo J 1996;15:192–198 [CrossRef]
    [Google Scholar]
  37. Viburiene R, Vik A, Koomey M, Borud B. Allelic variation in a simple sequence repeat element of neisserial pglB2 and its consequences for protein expression and protein glycosylation. J Bacteriol 2013;195:3476–3485 [CrossRef]
    [Google Scholar]
  38. Saunders NJ, Jeffries AC, Peden JF, Hood DW, Tettelin H et al. Repeat-associated phase variable genes in the complete genome sequence of Neisseria meningitidis strain MC58. Mol Microbiol 2000;37:207–215 [CrossRef]
    [Google Scholar]
  39. Zelewska MA, Pulijala M, Spencer-Smith R, Mahmood H-T-NA, Norman B et al. Phase variable DNA repeats in Neisseria gonorrhoeae influence transcription, translation, and protein sequence variation. Microb Genom 2016;2:e000078 [CrossRef]
    [Google Scholar]
  40. Greenwood B. Manson lecture: meningococcal meningitis in Africa. Trans R Soc Trop Med Hyg 1999;93:341–353 [CrossRef]
    [Google Scholar]
  41. Jarvis GA, Vedros NA. Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation. Infect Immun 1987;55:174–180
    [Google Scholar]
  42. Clemence MEA, Maiden MCJ, Harrison OB. Characterization of capsule genes in non-pathogenic Neisseria species. Microb Genom 2018;4:e000208 [CrossRef]
    [Google Scholar]
  43. Linz B, Schenker M, Zhu P, Achtman M. Frequent interspecific genetic exchange between commensal neisseriae and Neisseria meningitidis. Mol Microbiol 2000;36:1049–1058 [CrossRef]
    [Google Scholar]
  44. Alfsnes K, Frye SA, Eriksson J, Eldholm V, Brynildsrud OB et al. A genomic view of experimental intraspecies and interspecies transformation of a rifampicin-resistance allele into Neisseria meningitidis. Microb Genom 2018;4:e000222 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/mgen/10.1099/mgen.0.000290
Loading
/content/journal/mgen/10.1099/mgen.0.000290
Loading

Data & Media loading...

Supplementary material 1

PDF

Supplementary material 2

Most Cited This Month

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