1887

Abstract

The molecular diversity of a novel antigen, encoded by the ORF NMB0088 of MC58 (FadL-like protein), was assessed in a panel of 64 diverse meningococcal strains. The panel consisted of strains belonging to different serogroups, serotypes, serosubtypes and MLST sequence types, of different clinical sources, years and countries of isolation. Based on the sequence variability of the protein, the FadL-like protein has been divided into four variant groups in this species. Antigen variants were associated with specific serogroups and MLST clonal complexes. Maximum-likelihood analyses were used to determine the relationships among sequences and to compare the selection pressures acting on the encoded protein. Furthermore, a model of population genetics and molecular evolution was used to detect natural selection in DNA sequences using the non-synonymous : synonymous substitution (  :  ) ratio. The meningococcal sequences were also compared with those of the related surface protein in non-pathogenic commensal species to investigate potential horizontal gene transfer. The gene was subject to only weak positive selection pressure and was less diverse than meningococcal major outer-membrane proteins. The majority of the variability in was due to recombination among existing alleles from the same or related species that resulted in a discrete mosaic structure in the meningococcal population. In general, the population structuring observed based on the FadL-like membrane protein indicates that it is under intermediate immune selection. However, the emergence of a new subvariant within the hyperinvasive lineages demonstrates the phenotypic adaptability of , probably in response to selective pressure.

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2010-12-01
2019-10-14
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References

  1. Bambini, S., Muzzi, A., Olcen, P., Rappuoli, R., Pizza, M. & Comanducci, M. ( 2009; ). Distribution and genetic variability of three vaccine components in a panel of strains representative of the diversity of serogroup B meningococcus. Vaccine 27, 2794–2803.[CrossRef]
    [Google Scholar]
  2. Beernink, P. T. & Granoff, D. M. ( 2009; ). The modular architecture of meningococcal factor H-binding protein. Microbiology 155, 2873–2883.[CrossRef]
    [Google Scholar]
  3. Bennett, J. S., Thompson, E. A., Kriz, P., Jolley, K. A. & Maiden, M. C. ( 2009; ). A common gene pool for the Neisseria FetA antigen. Int J Med Microbiol 299, 133–139.[CrossRef]
    [Google Scholar]
  4. Bentley, S. D., Vernikos, G. S., Snyder, L. A., Churcher, C., Arrowsmith, C., Chillingworth, T., Cronin, A., Davis, P. H., Holroyd, N. E. & other authors ( 2007; ). Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet 3, e23.[CrossRef]
    [Google Scholar]
  5. Brehony, C., Wilson, D. J. & Maiden, M. C. ( 2009; ). Variation of the factor H-binding protein of Neisseria meningitidis. Microbiology 155, 4155–4169.[CrossRef]
    [Google Scholar]
  6. Callaghan, M. J., Jolley, K. A. & Maiden, M. C. ( 2006; ). Opacity-associated adhesin repertoire in hyperinvasive Neisseria meningitidis. Infect Immun 74, 5085–5094.[CrossRef]
    [Google Scholar]
  7. Callaghan, M. J., Buckee, C. O., Jolley, K. A., Kriz, P., Maiden, M. C. & Gupta, S. ( 2008; ). The effect of immune selection on the structure of the meningococcal opa protein repertoire. PLoS Pathog 4, e1000020.[CrossRef]
    [Google Scholar]
  8. Caugant, D. A., Mocca, L. F., Frasch, C. E., Froholm, L. O., Zollinger, W. D. & Selander, R. K. ( 1987; ). Genetic structure of Neisseria meningitidis populations in relation to serogroup, serotype, and outer membrane protein pattern. J Bacteriol 169, 2781–2792.
    [Google Scholar]
  9. Chung, G. T., Yoo, J. S., Oh, H. B., Lee, Y. S., Cha, S. H., Kim, S. J. & Yoo, C. K. ( 2008; ). Complete genome sequence of Neisseria gonorrhoeae NCCP11945. J Bacteriol 190, 6035–6036.[CrossRef]
    [Google Scholar]
  10. Derrick, J. P., Urwin, R., Suker, J., Feavers, I. M. & Maiden, M. C. ( 1999; ). Structural and evolutionary inference from molecular variation in Neisseria porins. Infect Immun 67, 2406–2413.
    [Google Scholar]
  11. Didelot, X. & Falush, D. ( 2007; ). Inference of bacterial microevolution using multilocus sequence data. Genetics 175, 1251–1266.
    [Google Scholar]
  12. Dyet, K. H. & Martin, D. R. ( 2005; ). Sequence variation in the porB gene from B:P1.4 meningococci causing New Zealand's epidemic. J Clin Microbiol 43, 838–842.[CrossRef]
    [Google Scholar]
  13. Evans, N. J., Harrison, O. B., Clow, K., Derrick, J. P., Feavers, I. M. & Maiden, M. C. ( 2010; ). Variation and molecular evolution of HmbR, the Neisseria meningitidis haemoglobin receptor. Microbiology 156, 1384–1393.[CrossRef]
    [Google Scholar]
  14. Feavers, I. M. & Pizza, M. ( 2009; ). Meningococcal protein antigens and vaccines. Vaccine 27 ((Suppl. 2), ), B42–B50.[CrossRef]
    [Google Scholar]
  15. Feavers, I. M., Heath, A. B., Bygraves, J. A. & Maiden, M. C. ( 1992; ). Role of horizontal genetic exchange in the antigenic variation of the class 1 outer membrane protein of Neisseria meningitidis. Mol Microbiol 6, 489–495.[CrossRef]
    [Google Scholar]
  16. Finne, J., Bitter-Suermann, D., Goridis, C. & Finne, U. ( 1987; ). An IgG monoclonal antibody to group B meningococci cross-reacts with developmentally regulated polysialic acid units of glycoproteins in neural and extraneural tissues. J Immunol 138, 4402–4407.
    [Google Scholar]
  17. Frasch, C. E., Borrow, R. & Donnelly, J. ( 2009; ). Bactericidal antibody is the immunologic surrogate of protection against meningococcal disease. Vaccine 27 ((Suppl. 2), ), B112–B116.[CrossRef]
    [Google Scholar]
  18. Guindon, S. & Gascuel, O. ( 2003; ). A simple, fast, and accurate algorithm to estimate large phylogenies by maximum likelihood. Syst Biol 52, 696–704.[CrossRef]
    [Google Scholar]
  19. Gupta, S. & Maiden, M. C. ( 2001; ). Exploring the evolution of diversity in pathogen populations. Trends Microbiol 9, 181–185.[CrossRef]
    [Google Scholar]
  20. Gupta, S., Maiden, M. C., Feavers, I. M., Nee, S., May, R. M. & Anderson, R. M. ( 1996; ). The maintenance of strain structure in populations of recombining infectious agents. Nat Med 2, 437–442.[CrossRef]
    [Google Scholar]
  21. Häyrinen, J., Jennings, H., Raff, H. V., Rougon, G., Hanai, N., Gerardy-Schahn, R. & Finne, J. ( 1995; ). Antibodies to polysialic acid and its N-propyl derivative: binding properties and interaction with human embryonal brain glycopeptides. J Infect Dis 171, 1481–1490.[CrossRef]
    [Google Scholar]
  22. Hearn, E. M., Patel, D. R. & van den Berg, B. ( 2008; ). Outer-membrane transport of aromatic hydrocarbons as a first step in biodegradation. Proc Natl Acad Sci U S A 105, 8601–8606.[CrossRef]
    [Google Scholar]
  23. Huson, D. H. & Bryant, D. ( 2006; ). Application of phylogenetic networks in evolutionary studies. Mol Biol Evol 23, 254–267.
    [Google Scholar]
  24. Jódar, L., Feavers, I. M., Salisbury, D. & Granoff, D. M. ( 2002; ). Development of vaccines against meningococcal disease. Lancet 359, 1499–1508.[CrossRef]
    [Google Scholar]
  25. Keane, T. M., Creevey, C. J., Pentony, M. M., Naughton, T. J. & Mclnerney, J. O. ( 2006; ). Assessment of methods for amino acid matrix selection and their use on empirical data shows that ad hoc assumptions for choice of matrix are not justified. BMC Evol Biol 6, 29.[CrossRef]
    [Google Scholar]
  26. Kosakovsky Pond, S. L. & Frost, S. D. ( 2005a; ). Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22, 1208–1222.[CrossRef]
    [Google Scholar]
  27. Kosakovsky Pond, S. L. & Frost, S. D. ( 2005b; ). Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21, 2531–2533.[CrossRef]
    [Google Scholar]
  28. Kosakovsky Pond, S. L., Posada, D., Gravenor, M. B., Woelk, C. H. & Frost, S. D. ( 2006; ). Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23, 1891–1901.[CrossRef]
    [Google Scholar]
  29. Kumar, S., Tamura, K. & Nei, M. ( 2004; ). MEGA3: integrated software for Molecular Evolutionary Genetics Analysis and sequence alignment. Brief Bioinform 5, 150–163.[CrossRef]
    [Google Scholar]
  30. Lanave, C., Preparata, G., Saccone, C. & Serio, G. ( 1984; ). A new method for calculating evolutionary substitution rates. J Mol Evol 20, 86–93.[CrossRef]
    [Google Scholar]
  31. Lewis, S., Sadarangani, M., Hoe, J. C. & Pollard, A. J. ( 2009; ). Challenges and progress in the development of a serogroup B meningococcal vaccine. Expert Rev Vaccines 8, 729–745.[CrossRef]
    [Google Scholar]
  32. Librado, P. & Rozas, J. ( 2009; ). DnaSP v5: a software for comprehensive analysis of DNA polymorphism data. Bioinformatics 25, 1451–1452.[CrossRef]
    [Google Scholar]
  33. Linz, B., Schenker, M., Zhu, P. & Achtman, M. ( 2000; ). Frequent interspecific genetic exchange between commensal neisseriae and Neisseria meningitidis. Mol Microbiol 36, 1049–1058.[CrossRef]
    [Google Scholar]
  34. Liu, S. V., Saunders, N. J., Jeffries, A. & Rest, R. F. ( 2002; ). Genome analysis and strain comparison of Correia repeats and Correia repeat-enclosed elements in pathogenic Neisseria. J Bacteriol 184, 6163–6173.[CrossRef]
    [Google Scholar]
  35. Martin, D. R., Ruijne, N., McCallum, L., O'Hallahan, J. & Oster, P. ( 2006; ). The VR2 epitope on the PorA P1.7-2,4 protein is the major target for the immune response elicited by the strain-specific group B meningococcal vaccine MeNZB. Clin Vaccine Immunol 13, 486–491.[CrossRef]
    [Google Scholar]
  36. Mes, T. H. & van Putten, J. P. ( 2007; ). Positively selected codons in immune-exposed loops of the vaccine candidate OMP-P1 of Haemophilus influenzae. J Mol Evol 64, 411–422.[CrossRef]
    [Google Scholar]
  37. Mitka, M. ( 2005; ). New vaccine should ease meningitis fears. JAMA 293, 1433–1434.[CrossRef]
    [Google Scholar]
  38. Nei, M. & Gojobori, T. ( 1986; ). Simple methods for estimating the numbers of synonymous and non-synonymous nucleotide substitutions. Mol Biol Evol 3, 418–426.
    [Google Scholar]
  39. Nielsen, R. & Yang, Z. ( 1998; ). Likelihood models for detecting positively selected amino acid sites and applications to the HIV-1 envelope gene. Genetics 148, 929–936.
    [Google Scholar]
  40. Pajón, R., Yero, D., Niebla, O., Climent, Y., Sardiñas, G., García, D., Perera, Y., Llanes, A., Delgado, M. & other authors ( 2009; ). Identification of new meningococcal serogroup B surface antigens through a systematic analysis of neisserial genomes. Vaccine 28, 532–541.[CrossRef]
    [Google Scholar]
  41. Parkhill, J., Achtman, M., James, K. D., Bentley, S. D., Churcher, C., Klee, S. R., Morelli, G., Basham, D., Brown, D. & other authors ( 2000; ). Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404, 502–506.[CrossRef]
    [Google Scholar]
  42. Peeters, C. C., Claassen, I. J., Schuller, M., Kersten, G. F., van der Voort, E. M. & Poolman, J. T. ( 1999; ). Immunogenicity of various presentation forms of PorA outer membrane protein of Neisseria meningitidis in mice. Vaccine 17, 2702–2712.[CrossRef]
    [Google Scholar]
  43. Peng, J., Yang, L., Yang, F., Yang, J., Yan, Y., Nie, H., Zhang, X., Xiong, Z., Jiang, Y. & other authors ( 2008; ). Characterization of ST-4821 complex, a unique Neisseria meningitidis clone. Genomics 91, 78–87.[CrossRef]
    [Google Scholar]
  44. Pizza, M., Scarlato, V., Masignani, V., Giuliani, M. M., Arico, B., Comanducci, M., Jennings, G. T., Baldi, L., Bartolini, E. & other authors ( 2000; ). Identification of vaccine candidates against serogroup B meningococcus by whole-genome sequencing. Science 287, 1816–1820.[CrossRef]
    [Google Scholar]
  45. Rosenstein, N. E., Perkins, B. A., Stephens, D. S., Popovic, T. & Hughes, J. M. ( 2001; ). Meningococcal disease. N Engl J Med 344, 1378–1388.[CrossRef]
    [Google Scholar]
  46. Sadarangani, M. & Pollard, A. J. ( 2010; ). Serogroup B meningococcal vaccines – an unfinished story. Lancet Infect Dis 10, 112–124.[CrossRef]
    [Google Scholar]
  47. Sardiñas, G., Yero, D., Climent, Y., Caballero, E., Cobas, K. & Niebla, O. ( 2009; ). Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential. J Med Microbiol 58, 196–208.[CrossRef]
    [Google Scholar]
  48. Spratt, B. G., Bowler, L. D., Zhang, Q. Y., Zhou, J. & Smith, J. M. ( 1992; ). Role of interspecies transfer of chromosomal genes in the evolution of penicillin resistance in pathogenic and commensal Neisseria species. J Mol Evol 34, 115–125.
    [Google Scholar]
  49. Suker, J., Feavers, I. M., Achtman, M., Morelli, G., Wang, J. F. & Maiden, M. C. ( 1994; ). The porA gene in serogroup A meningococci: evolutionary stability and mechanism of genetic variation. Mol Microbiol 12, 253–265.[CrossRef]
    [Google Scholar]
  50. Tettelin, H., Saunders, N. J., Heidelberg, J., Jeffries, A. C., Nelson, K. E., Eisen, J. A., Ketchum, K. A., Hood, D. W., Peden, J. F. & other authors ( 2000; ). Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809–1815.[CrossRef]
    [Google Scholar]
  51. Thompson, E. A., Feavers, I. M. & Maiden, M. C. ( 2003; ). Antigenic diversity of meningococcal enterobactin receptor FetA, a vaccine component. Microbiology 149, 1849–1858.[CrossRef]
    [Google Scholar]
  52. Uli, L., Castellanos-Serra, L., Betancourt, L., Dominguez, F., Barberá, R., Sotolongo, F., Guillén, G. & Pajón, F. R. ( 2006; ). Outer membrane vesicles of the VA-MENGOC-BC® vaccine against serogroup B of Neisseria meningitidis: analysis of protein components by two-dimensional gel electrophoresis and mass spectrometry. Proteomics 6, 3389–3399.[CrossRef]
    [Google Scholar]
  53. Urwin, R., Holmes, E. C., Fox, A. J., Derrick, J. P. & Maiden, M. C. ( 2002; ). Phylogenetic evidence for frequent positive selection and recombination in the meningococcal surface antigen PorB. Mol Biol Evol 19, 1686–1694.[CrossRef]
    [Google Scholar]
  54. Urwin, R., Russell, J. E., Thompson, E. A., Holmes, E. C., Feavers, I. M. & Maiden, M. C. ( 2004; ). Distribution of surface protein variants among hyperinvasive meningococci: implications for vaccine design. Infect Immun 72, 5955–5962.[CrossRef]
    [Google Scholar]
  55. van den Berg, B. ( 2005; ). The FadL family: unusual transporters for unusual substrates. Curr Opin Struct Biol 15, 401–407.[CrossRef]
    [Google Scholar]
  56. van den Berg, B., Black, P. N., Clemons, W. M., Jr & Rapoport, T. A. ( 2004; ). Crystal structure of the long-chain fatty acid transporter FadL. Science 304, 1506–1509.[CrossRef]
    [Google Scholar]
  57. van den Dobbelsteen, G. P. J. M., van Dijken, H. H., Pillai, S. & van Alphen, L. ( 2007; ). Immunogenicity of a combination vaccine containing pneumococcal conjugates and meningococcal PorA OMVs. Vaccine 25, 2491–2496.[CrossRef]
    [Google Scholar]
  58. Vaughan, T. E., Skipp, P. J., O'Connor, C. D., Hudson, M. J., Vipond, R., Elmore, M. J. & Gorringe, A. R. ( 2006; ). Proteomic analysis of Neisseria lactamica and Neisseria meningitidis outer membrane vesicle vaccine antigens. Vaccine 24, 5277–5293.[CrossRef]
    [Google Scholar]
  59. Vipond, C., Suker, J., Jones, C., Tang, C., Feavers, I. M. & Wheeler, J. X. ( 2006; ). Proteomic analysis of a meningococcal outer membrane vesicle vaccine prepared from the group B strain NZ98/254. Proteomics 6, 3400–3413.[CrossRef]
    [Google Scholar]
  60. Welsch, J. A., Rossi, R., Comanducci, M. & Granoff, D. M. ( 2004; ). Protective activity of monoclonal antibodies to genome-derived neisserial antigen 1870, a Neisseria meningitidis candidate vaccine. J Immunol 172, 5606–5615.[CrossRef]
    [Google Scholar]
  61. Williams, J. N., Skipp, P. J., Humphries, H. E., Christodoulides, M., O'Connor, C. D. & Heckels, J. E. ( 2007; ). Proteomic analysis of outer membranes and vesicles from wild-type serogroup B Neisseria meningitidis and a lipopolysaccharide-deficient mutant. Infect Immun 75, 1364–1372.[CrossRef]
    [Google Scholar]
  62. Wilson, D. J. & McVean, G. ( 2006; ). Estimating diversifying selection and functional constraint in the presence of recombination. Genetics 172, 1411–1425.
    [Google Scholar]
  63. Yang, Z. ( 1994; ). Estimating the pattern of nucleotide substitution. J Mol Evol 39, 105–111.
    [Google Scholar]
  64. Yang, Z. ( 2007; ). PAML 4: phylogenetic analysis by maximum likelihood. Mol Biol Evol 24, 1586–1591.[CrossRef]
    [Google Scholar]
  65. Yang, Z., Nielsen, R., Goldman, N. & Pedersen, A. M. ( 2000; ). Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 155, 431–449.
    [Google Scholar]
  66. Yang, Z., Wong, W. S. & Nielsen, R. ( 2005; ). Bayes empirical Bayes inference of amino acid sites under positive selection. Mol Biol Evol 22, 1107–1118.[CrossRef]
    [Google Scholar]
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vol. , part 12, pp. 3596 - 3608

Meningococcal strains used in this study [ PDF] (10 kb)



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