1887

Abstract

During periods of endemic disease, about 10 % of the general population harbour in the nasopharynx. Since is a strict human pathogen and most patients have not been in contact with other cases, asymptomatic carriers are presumably the major source of the pathogenic strains. Most carrier isolates are shown to lack capsule production. The capsule deficient state of meningococcal strains in the nasopharynx may aid evasion of the human immune defence and hence be selected to survive nasopharyngeal colonization. Carriage itself can be an immunizing process resulting in systemic protective antibody responses. Frequent nasopharyngeal colonization with related bacteria like improves natural immunity to meningococci by the formation of cross-reacting antibodies. While most meningococcal strains recovered from patients belong to a limited number of clonal groups worldwide, strains isolated from carriers comprise numerous genotypes, with only a small proportion of the strains representing invasive clones. During the carriage state, co-colonization with other pathogenic and non-pathogenic bacteria may lead to genetic exchange, which may result in the emergence of new meningococcal clones. The high diversity of meningococcal carrier strains, compared with hypervirulent strains, supports the idea that transmissibility, not invasion, is essential in the life cycle of .

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2004-09-01
2019-11-14
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References

  1. Abramson, J. S. & Spika, J. S. ( 1985;). Persistence of Neisseria meningitidis in the upper respiratory tract after intravenous antibiotic therapy for systemic meningococcal disease. J Infect Dis 151, 370–371.[CrossRef]
    [Google Scholar]
  2. Ala'Aldeen, D. A., Neal, K. R., Ait-Tahar, K., Nguyen-Van-Tam, J. S., English, A., Falla, T. J., Hawkey, P. M. & Slack, R. C. ( 2000;). Dynamics of meningococcal long-term carriage among university students and their implications for mass vaccination. J Clin Microbiol 38, 2311–2316.
    [Google Scholar]
  3. Andoh, A., Fujiyama, Y., Kimura, T., Uchihara, H., Sakumoto, H., Okabe, H. & Bamaba, T. ( 1997;). Molecular characterization of complement components (C3, C4, and factor B) in human saliva. J Clin Immunol 17, 404–407.[CrossRef]
    [Google Scholar]
  4. Arreaza, L., Salcedo, C., Alcala, B. & Vazquez, J. A. ( 2002;). What about antibiotic resistance in Neisseria lactamica? J Antimicrob Chemother 49, 545–547.[CrossRef]
    [Google Scholar]
  5. Bäckman, A., Orvelid, P., Vazquez, J. A., Sköld, O. & Olcén, P. ( 2000;). Complete sequence of a β-lactamase-encoding plasmid in Neisseria meningitidis. Antimicrob Agents Chemother 44, 210–212.[CrossRef]
    [Google Scholar]
  6. Bitter, W., Koster, M., Latijnhouwers, M., de Cock, H. & Tommassen, J. ( 1998;). Formation of oligomeric rings by XcpQ and PilQ, which are involved in protein transport across the outer membrane of Pseudomonas aeruginosa. Mol Microbiol 27, 209–219.[CrossRef]
    [Google Scholar]
  7. Blackwell, C. C., Weir, D. M., James, V. S., Todd, W. T., Banatvala, N., Chaudhuri, A. K., Gray, H. G., Thomson, E. J. & Fallon, R. J. ( 1990;). Secretor status, smoking and carriage of Neisseria meningitidis. Epidemiol Infect 104, 203–209.[CrossRef]
    [Google Scholar]
  8. Blackwell, C. C., Tzanakaki, G., Kremastinou, J., Weir, D. M., Vakalis, N., Elton, R. A., Mentis, A. & Fatouros, N. ( 1992;). Factors affecting carriage of Neisseria meningitidis among Greek military recruits. Epidemiol Infect 108, 441–448.[CrossRef]
    [Google Scholar]
  9. Brandtzaeg, P., Bjerre, A., Øvstebø, R., Brusletto, B., Joø, G. B. & Kierulf, P. ( 2001;). Neisseria meningitidis lipopolysaccharides in human pathology. J Endotoxin Res 7, 401–420.
    [Google Scholar]
  10. Broome, C. V. ( 1986;). The carrier state: Neisseria meningitidis. J Antimicrob Chemother 18, 25–34.
    [Google Scholar]
  11. Cardenosa, N., Dominguez, A., Orcau, A., Panella, H., Godoy, P., Minguell, S., Camps, N. & Vazquez, J. A. ( 2001;). Carriers of Neisseria meningitidis in household contacts of meningococcal disease cases in Catalonia (Spain). Eur J Epidemiol 17, 877–884.[CrossRef]
    [Google Scholar]
  12. Cartwright, K. ( 1995;). Meningococcal carriage and disease. In Meningococcal Disease, pp. 115–146. Edited by K. Cartwright. Chichester, UK: Wiley & Sons.
  13. Cartwright, K. A., Stuart, J. M., Jones, D. M. & Noah, N. D. ( 1987;). The Stonehouse survey: nasopharyngeal carriage of meningococci and Neisseria lactamica. Epidemiol Infect 99, 591–601.[CrossRef]
    [Google Scholar]
  14. Caugant, D. A. ( 1998;). Population genetics and molecular epidemiology of Neisseria meningitidis. APMIS 106, 505–525.[CrossRef]
    [Google Scholar]
  15. Caugant, D. A., Kristiansen, B. E., Frøholm, L. O., Bøvre, K. & Selander, R. K. ( 1988;). Clonal diversity of Neisseria meningitidis from a population of asymptomatic carriers. Infect Immun 56, 2060–2068.
    [Google Scholar]
  16. Caugant, D. A., Høiby, E. A., Rosenqvist, E., Frøholm, L. O. & Selander, R. K. ( 1992;). Transmission of Neisseria meningitidis among asymptomatic military recruits and antibody analysis. Epidemiol Infect 109, 241–253.[CrossRef]
    [Google Scholar]
  17. Caugant, D. A., Høiby, E. A., Magnus, P., Scheel, O., Hoel, T., Bjune, G., Wedege, E., Eng, J. & Frøholm, L. O. ( 1994;). Asymptomatic carriage of Neisseria meningitidis in a randomly sampled population. J Clin Microbiol 32, 323–330.
    [Google Scholar]
  18. Claus, H., Swiderek, H., Frosch, M. & Vogel, U. ( 2002a;). Meningococcal sequence typing using microarrays. In Abstracts of the 13th International Pathogenic Neisseria Conference, abstract 341. Edited by D. A. Caugant & E. Wedege. Oslo: Norwegian Institute of Public Health.
  19. Claus, H., Maiden, M. C., Maag, R., Frosch, M. & Vogel, U. ( 2002b;). Many carried meningococci lack the genes required for capsule synthesis and transport. Microbiology 148, 1813–1819.
    [Google Scholar]
  20. Claus, H., Borrow, R., Achtman, M., Morelli, G., Kantelberg, C., Longworth, E., Frosch, M. & Vogel, U. ( 2004;). Genetics of capsule O-acetylation in serogroup C, W-135 and Y meningococci. Mol Microbiol 51, 227–239.
    [Google Scholar]
  21. Cooke, R. P., Riordan, T., Jones, D. M. & Painter, M. J. ( 1989;). Secondary cases of meningococcal infection among close family and household contacts in England and Wales, 1984–7. BMJ 298, 555–558.[CrossRef]
    [Google Scholar]
  22. Cunningham, R., Mathews, R., Lewendon, G., Harrison, S. & Stuart, J. M. ( 2001;). Improved rate of isolation of Neisseria meningitidis by direct plating of pharyngeal swabs. J Clin Microbiol 39, 4575–4576.[CrossRef]
    [Google Scholar]
  23. D'Amelio, R., Agostoni, A., Biselli, R. & 7 other authors ( 1992;). Complement deficiency and antibody profile in survivors of meningococcal meningitis due to common serogroups in Italy. Scand J Immunol 35, 589–595.[CrossRef]
    [Google Scholar]
  24. Davidsen, T., Rodland, E. A., Lagesen, K., Seeberg, E., Rognes, T. & Tonjum, T. ( 2004;). Biased distribution of DNA uptake sequences towards genome maintenance genes. Nucleic Acids Res 32, 1050–1058.[CrossRef]
    [Google Scholar]
  25. Davies, A. L., O'Flanagan, D., Salmon, R. L. & Coleman, T. J. ( 1996;). Risk factors for Neisseria meningitidis carriage in a school during a community outbreak of meningococcal infection. Epidemiol Infect 117, 259–266.[CrossRef]
    [Google Scholar]
  26. Deal, W. B. & Sanders, E. ( 1969;). Efficacy of rifampin in treatment of meningococcal carriers. N Engl J Med 281, 641–645.[CrossRef]
    [Google Scholar]
  27. Deghmane, A. E., Petit, S., Topilko, A., Pereira, Y., Giorgini, D., Larribe, M. & Taha, M. K. ( 2000;). Intimate adhesion of Neisseria meningitidis to human epithelial cells is under the control of the crgA gene, a novel LysR-type transcriptional regulator. EMBO J 19, 1068–1078.[CrossRef]
    [Google Scholar]
  28. Deghmane, A. E., Giorgini, D., Larribe, M., Alonso, J. M. & Taha, M. K. ( 2002;). Down-regulation of pili and capsule of Neisseria meningitidis upon contact with epithelial cells is mediated by CrgA regulatory protein. Mol Microbiol 43, 1555–1564.[CrossRef]
    [Google Scholar]
  29. Dehio, C., Gray-Owen, S. D. & Meyer, T. F. ( 1998;). The role of neisserial Opa proteins in interactions with host cells. Trends Microbiol 6, 489–495.[CrossRef]
    [Google Scholar]
  30. Dillon, J. R., Pauze, M. & Yeung, K. H. ( 1983;). Spread of penicillinase-producing and transfer plasmids from the gonococcus to Neisseria meningitidis. Lancet 1, 779–781.
    [Google Scholar]
  31. Di Martino, M., Cali, G., Astorre, P., Usai, G. C., Ferrari, R. & Stroffolini, T. ( 1990;). Meningococcal carriage and vaccination in army recruits in Italy. Boll Ist Sieroter Milan 69, 357–359.
    [Google Scholar]
  32. Djupesland, P., Bjune, G., Aanosen, N. O., Borchgrevink, H. M., Mundal, R. & Høiby, E. A. ( 1990;). Systemic menningococcal disease in the Norwegian Army. Nord Med 105, 179–181 (in Norwegian).
    [Google Scholar]
  33. Dolan-Livengood, J. M., Miller, Y. K., Martin, L. E., Urwin, R. & Stephens, D. S. ( 2003;). Genetic basis for nongroupable Neisseria meningitidis. J Infect Dis 187, 1616–1628.[CrossRef]
    [Google Scholar]
  34. Edwards, U., Muller, A., Hammerschmidt, S., Gerardy-Schahn, R. & Frosch, M. ( 1994;). Molecular analysis of the biosynthesis pathway of the α-2,8 polysialic acid capsule by Neisseria meningitidis serogroup B. Mol Microbiol 14, 141–149.[CrossRef]
    [Google Scholar]
  35. Fairley, C. K., Begg, N., Borrow, R., Fox, A. J., Jones, D. M. & Cartwright, K. ( 1996;). Conjugate meningococcal serogroup A and C vaccine: reactogenicity and immunogenicity in United Kingdom infants. J Infect Dis 174, 1360–1363.[CrossRef]
    [Google Scholar]
  36. Feil, E. J., Maiden, M. C., Achtman, M. & Spratt, B. G. ( 1999;). The relative contributions of recombination and mutation to the divergence of clones of Neisseria meningitidis. Mol Biol Evol 16, 1496–1502.[CrossRef]
    [Google Scholar]
  37. Fermer, C. & Swedberg, G. ( 1997;). Adaptation to sulfonamide resistance in Neisseria meningitidis may have required compensatory changes to retain enzyme function: kinetic analysis of dihydropteroate synthases from N.meningitidis expressed in a knockout mutant of Escherichia coli. J Bacteriol 179, 831–837.
    [Google Scholar]
  38. Fermer, C., Kristiansen, B. E., Sköld, O. & Swedberg, G. ( 1995;). Sulfonamide resistance in Neisseria meningitidis as defined by site-directed mutagenesis could have its origin in other species. J Bacteriol 177, 4669–4675.
    [Google Scholar]
  39. Fernandez, S., Arreaza, L., Santiago, I., Malvar, A., Berron, S., Vazquez, J. A. & Hervada, X. ( 2003;). Impact of meningococcal vaccination with combined serogroups A and C polysaccharide vaccine on carriage of Neisseria meningitidis C. J Med Microbiol 52, 75–77.[CrossRef]
    [Google Scholar]
  40. Fijen, C. A., Kuijper, E. J., Hannema, A. J., Sjöholm, A. G. & van Putten, J. P. ( 1989;). Complement deficiencies in patients over ten years old with meningococcal disease due to uncommon serogroups. Lancet 2, 585–588.
    [Google Scholar]
  41. Frasch, C. E., Zollinger, W. D. & Poolman, J. T. ( 1985;). Serotype antigens of Neisseria meningitidis and a proposed scheme for designation of serotypes. Rev Infect Dis 7, 504–510.[CrossRef]
    [Google Scholar]
  42. Frosch, M. & Muller, A. ( 1993;). Phospholipid substitution of capsular polysaccharides and mechanisms of capsule formation in Neisseria meningitidis. Mol Microbiol 8, 483–493.[CrossRef]
    [Google Scholar]
  43. Frosch, M., Weisgerber, C. & Meyer, T. F. ( 1989;). Molecular characterization and expression in Escherichia coli of the gene complex encoding the polysaccharide capsule of Neisseria meningitidis group B. Proc Natl Acad Sci U S A 86, 1669–1673.[CrossRef]
    [Google Scholar]
  44. Frosch, M., Edwards, U., Bousset, K., Krausse, B. & Weisgerber, C. ( 1991;). Evidence for a common molecular origin of the capsule gene loci in gram-negative bacteria expressing group II capsular polysaccharides. Mol Microbiol 5, 1251–1263.[CrossRef]
    [Google Scholar]
  45. Frosch, M., Muller, D., Bousset, K. & Muller, A. ( 1992;). Conserved outer membrane protein of Neisseria meningitidis involved in capsule expression. Infect Immun 60, 798–803.
    [Google Scholar]
  46. Gotschlich, E. C., Goldschneider, I. & Artenstein, M. S. ( 1969;). Human immunity to the meningococcus.V. The effect of immunization with meningococcal group C polysaccharide on the carrier state. J Exp Med 129, 1385–1395.[CrossRef]
    [Google Scholar]
  47. Gray-Owen, S. D. & Schryvers, A. B. ( 1996;). Bacterial transferrin and lactoferrin receptors. Trends Microbiol 4, 185–191.[CrossRef]
    [Google Scholar]
  48. Griffiss, J. M. ( 1995;). Mechanism of host immunity. In Meningococcal Disease, pp. 36–70. Edited by K. Cartwright. Chichester, UK: Wiley & Sons.
  49. Griffiss, J. M., Schneider, H., Mandrell, R. E., Yamasaki, R., Jarvis, G. A., Kim, J. J., Gibson, B. W., Hamadeh, R. & Apicella, M. A. ( 1988;). Lipooligosaccharides: the principal glycolipids of the neisserial outer membrane. Rev Infect Dis 10, S287–S295.[CrossRef]
    [Google Scholar]
  50. Hammerschmidt, S., Birkholz, C., Zahringer, U., Robertson, B. D., van Putten, J., Ebeling, O. & Frosch, M. ( 1994;). Contribution of genes from the capsule gene complex (cps) to lipooligosaccharide biosynthesis and serum resistance in Neisseria meningitidis. Mol Microbiol 11, 885–896.[CrossRef]
    [Google Scholar]
  51. Hammerschmidt, S., Muller, A., Sillmann, H. & 7 other authors ( 1996;). Capsule phase variation in Neisseria meningitidis serogroup B by slipped-strand mispairing in the polysialyltransferase gene (siaD): correlation with bacterial invasion and the outbreak of meningococcal disease. Mol Microbiol 20, 1211–1220.[CrossRef]
    [Google Scholar]
  52. Hassan-King, M. K., Wall, R. A. & Greenwood, B. M. ( 1988;). Meningococcal carriage, meningococcal disease and vaccination. J Infect 16, 55–59.[CrossRef]
    [Google Scholar]
  53. Hitchcock, P. J. ( 1989;). Unified nomenclature for pathogenic Neisseria species. Clin Microbiol Rev 2 (Suppl.), S64–S65.
    [Google Scholar]
  54. Hobbs, M. M., Seiler, A., Achtman, M. & Cannon, J. G. ( 1994;). Microevolution within a clonal population of pathogenic bacteria: recombination, gene duplication and horizontal genetic exchange in the opa gene family of Neisseria meningitidis. Mol Microbiol 12, 171–180.[CrossRef]
    [Google Scholar]
  55. Jackson, L. A., Alexander, E. R., Debolt, C. A., Swenson, P. D., Boase, J., McDowell, M. G., Reeves, M. W. & Wenger, J. D. ( 1996;). Evaluation of the mass chemoprophylaxis during a school outbreak of enzyme type 5 serogroup B meningococcal disease. Pediatr Infect Dis J 15, 992–998.[CrossRef]
    [Google Scholar]
  56. Jodar, L., Feavers, I. M., Salisbury, D. & Granoff, D. M. ( 2002;). Development of vaccines against meningococcal disease. Lancet 359, 1499–1508.[CrossRef]
    [Google Scholar]
  57. Johansson, L., Rytkonen, A., Bergman, P., Albiger, B., Källström, H., Hokfelt, T., Agerberth, B., Cattaneo, R. & Jonsson, A. B. ( 2003;). CD46 in meningococcal disease. Science 301, 373–375.[CrossRef]
    [Google Scholar]
  58. Jolley, K. A., Kalmusova, J., Feil, E. J., Gupta, S., Musilek, M., Kriz, P. & Maiden, M. C. ( 2000;). Carried meningococci in the Czech Republic: a diverse recombining population. J Clin Microbiol 38, 4492–4498.
    [Google Scholar]
  59. Jones, G. R., Christodoulides, M., Brooks, J. L., Miller, A. R., Cartwright, K. A. & Heckels, J. E. ( 1998;). Dynamics of carriage of Neisseria meningitidis in a group of military recruits: subtype stability and specificity of the immune response following colonization. J Infect Dis 178, 451–459.[CrossRef]
    [Google Scholar]
  60. Jordens, J. Z., Williams, J. N., Jones, G. R. & Heckels, J. E. ( 2002;). Detection of meningococcal carriage by culture and PCR of throat swabs and mouth gargles. J Clin Microbiol 40, 75–79.[CrossRef]
    [Google Scholar]
  61. Kahler, C. M. & Stephens, D. S. ( 1998;). Genetic basis for biosynthesis, structure, and function of meningococcal lipooligosaccharide (endotoxin). Crit Rev Microbiol 24, 281–334.
    [Google Scholar]
  62. Källström, H., Liszewski, M. K., Atkinson, J. P. & Jonsson, A. B. ( 1997;). Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol Microbiol 25, 639–647.[CrossRef]
    [Google Scholar]
  63. Källström, H., Islam, M. S., Berggren, P. O. & Jonsson, A. B. ( 1998;). Cell signaling by the type IV pili of pathogenic Neisseria. J Biol Chem 273, 21777–21782.[CrossRef]
    [Google Scholar]
  64. Kilian, M., Reinholdt, J., Lomholt, H., Poulsen, K. & Frandsen, E. V. ( 1996;). Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS 104, 321–338.[CrossRef]
    [Google Scholar]
  65. Koomey, M. ( 2001;). Implications of molecular contacts and signaling initiated by Neisseria gonorrhoeae. Curr Opin Microbiol 4, 53–57.[CrossRef]
    [Google Scholar]
  66. Kremastinou, J., Tzanakaki, G., Pagalis, A., Theodondou, M., Weir, D. M. & Blackwell, C. C. ( 1999;). Detection of IgG and IgM to meningococcal outer membrane proteins in relation to carriage of Neisseria meningitidis or Neisseria lactamica. FEMS Immunol Med Microbiol 24, 73–78.[CrossRef]
    [Google Scholar]
  67. Kremastinou, J., Tzanakaki, G., Levidiotou, S., Markou, F., Themeli, E., Voyiatzi, A., Psoma, E., Theodoridou, M. & Blackwell, C. C. ( 2003;). Carriage of Neisseria meningitidis and Neisseria lactamica in northern Greece. FEMS Immunol Med Microbiol 39, 23–29.[CrossRef]
    [Google Scholar]
  68. Kroll, J. S., Wilks, K. E., Farrant, J. L. & Langford, P. R. ( 1998;). Natural genetic exchange between Haemophilus and Neisseria: intergeneric transfer of chromosomal genes between major human pathogens. Proc Natl Acad Sci U S A 95, 12381–12385.[CrossRef]
    [Google Scholar]
  69. Larson, J. A., Higashi, D. L., Stojiljkovic, I. & So, M. ( 2002;). Replication of Neisseria meningitidis within epithelial cells requires TonB-dependent acquisition of host cell iron. Infect Immun 70, 1461–1467.[CrossRef]
    [Google Scholar]
  70. 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]
  71. Lomholt, H., Poulsen, K., Caugant, D. A. & Kilian, M. ( 1992;). Molecular polymorphism and epidemiology of Neisseria meningitidis immunoglobulin A1 proteases. Proc Natl Acad Sci U S A 89, 2120–2124.[CrossRef]
    [Google Scholar]
  72. Maiden, M. C., Suker, J., McKenna, A. J., Bygraves, J. A. & Feavers, I. M. ( 1991;). Comparison of the class 1 outer membrane proteins of eight serological reference strains of Neisseria meningitidis. Mol Microbiol 5, 727–736.[CrossRef]
    [Google Scholar]
  73. Maiden, M. C., Bygraves, J. A., McCarvil, J. & Feavers, I. M. ( 1992;). Identification of meningococcal serosubtypes by polymerase chain reaction. J Clin Microbiol 30, 2835–2841.
    [Google Scholar]
  74. Maiden, M. C., Bygraves, J. A., Feil, E. & 10 other authors ( 1998;). Multilocus sequence typing: a portable approach to the identification of clones within populations of pathogenic microorganisms. Proc Natl Acad Sci U S A 95, 3140–3145.[CrossRef]
    [Google Scholar]
  75. Maiden, M. C. J., Stuart, J. M., Bramley, J. C., MacLennan, J. M., Gray, S. & Andrew, N. ( 2002;). Carriage of serogroup C meningococci 1 year after meningococcal C conjugate polysaccharide vaccination. Lancet 359, 1829–1831.[CrossRef]
    [Google Scholar]
  76. McGuinness, B., Barlow, A. K., Clarke, I. N., Farley, J. E., Anilionis, A., Poolman, J. T. & Heckels, J. E. ( 1990;). Deduced amino acid sequences of class 1 protein (PorA) from three strains of Neisseria meningitidis.Synthetic peptides define the epitopes responsible for serosubtype specificity. J Exp Med 171, 1871–1882.[CrossRef]
    [Google Scholar]
  77. Mendelman, P. M., Campos, J., Chaffin, D. O., Serfass, D. A., Smith, A. L. & Saez-Nieto, J. A. ( 1988;). Relative penicillin G resistance in Neisseria meningitidis and reduced affinity of penicillin-binding protein 3. Antimicrob Agents Chemother 32, 706–709.[CrossRef]
    [Google Scholar]
  78. Merz, A. J. & So, M. ( 2000;). Interactions of pathogenic neisseriae with epithelial cell membranes. Annu Rev Cell Dev Biol 16, 423–457.[CrossRef]
    [Google Scholar]
  79. Merz, A. J., Rifenbery, D. B., Arvidson, C. G. & So, M. ( 1996;). Traversal of a polarized epithelium by pathogenic Neisseriae: facilitation by type IV pili and maintenance of epithelial barrier function. Mol Med 2, 745–754.
    [Google Scholar]
  80. Merz, A. J., Enns, C. A. & So, M. ( 1999;). Type IV pili of pathogenic Neisseriae elicit cortical plaque formation in epithelial cells. Mol Microbiol 32, 1316–1332.[CrossRef]
    [Google Scholar]
  81. Merz, A. J., So, M. & Sheetz, M. P. ( 2000;). Pilus retraction powers bacterial twitching motility. Nature 407, 98–102.[CrossRef]
    [Google Scholar]
  82. Neal, K. R., Nguyen-Van-Tam, J. S., Jeffrey, N., Slack, R. C., Madeley, R. J., Ait-Tahar, K., Job, K., Wale, M. C. & Ala'Aldeen, D. A. ( 2000;). Changing carriage rate of Neisseria meningitidis among university students during the first week of term: cross sectional study. BMJ 320, 846–849.[CrossRef]
    [Google Scholar]
  83. Nolte, O. ( 1997;). Rifampicin resistance in Neisseria meningitidis: evidence from a study of sibling strains, description of new mutations and notes on population genetics. J Antimicrob Chemother 39, 747–755.[CrossRef]
    [Google Scholar]
  84. Nurkka, A., MacLennan, J., Jantti, V., Obaro, S., Greenwood, B. & Kayhty, H. ( 2000;). Salivary antibody response to vaccination with meningococcal A/C polysaccharide vaccine in previously vaccinated and unvaccinated Gambian children. Vaccine 19, 547–556.[CrossRef]
    [Google Scholar]
  85. Olcén, P., Kjellander, J., Danielsson, D. & Lindquist, B. L. ( 1981;). Epidemiology of Neisseria meningitidis; prevalence and symptoms from the upper respiratory tract in family members to patients with meningococcal disease. Scand J Infect Dis 13, 105–109.[CrossRef]
    [Google Scholar]
  86. Oppenheim, B. A. ( 1997;). Antibiotic resistance in Neisseria meningitidis. Clin Infect Dis 24, (Suppl. 1), S98–S101.[CrossRef]
    [Google Scholar]
  87. Pohlner, J., Klauser, T., Kuttler, E. & Halter, R. ( 1992;). Sequence-specific cleavage of protein fusions using a recombinant Neisseria type 2 IgA protease. Biotechnology (N Y) 10, 799–804.[CrossRef]
    [Google Scholar]
  88. Pollard, A. J. & Frasch, C. ( 2001;). Development of natural immunity to Neisseria meningitidis. Vaccine 19, 1327–1346.[CrossRef]
    [Google Scholar]
  89. Poolman, J. T., van Der Ley, P. A. & Tommassen, J. ( 1995;). Surface structure and secreted products of meningococci. In Meningococcal Disease, pp. 21–34. Edited by K. Cartwright. Chichester, UK: Wiley & Sons.
  90. Porat, N., Apicella, M. A. & Blake, M. S. ( 1995;). A lipooligosaccharide-binding site on HepG2 cells similar to the gonococcal opacity-associated surface protein Opa. Infect Immun 63, 2164–2172.
    [Google Scholar]
  91. Pujol, C., Eugene, E., Marceau, M. & Nassif, X. ( 1999;). The meningococcal PilT protein is required for induction of intimate attachment to epithelial cells following pilus-mediated adhesion. Proc Natl Acad Sci U S A 96, 4017–4022.[CrossRef]
    [Google Scholar]
  92. Reller, L. B., MacGregor, R. R. & Beaty, H. N. ( 1973;). Bactericidal antibody after colonization with Neisseria meningitidis. J Infect Dis 127, 56–62.[CrossRef]
    [Google Scholar]
  93. Roberts, M. C. & Knapp, J. S. ( 1988;). Transfer of β-lactamase plasmids from Neisseria gonorrhoeae to Neisseria meningitidis and commensal Neisseria species by the 25.2-megadalton conjugative plasmid. Antimicrob Agents Chemother 32, 1430–1432.[CrossRef]
    [Google Scholar]
  94. Robinson, K., Neal, K. R., Howard, C. & 11 other authors ( 2002;). Characterization of humoral and cellular immune responses elicited by meningococcal carriage. Infect Immun 70, 1301–1309.[CrossRef]
    [Google Scholar]
  95. Rosenqvist, E., Bjune, G., Feiring, B., Eng, J., Frøholm, L. O., Høiby, A., Moe, B. & Nøkleby, H. ( 1994;). Changes in carrier status of Neisseria meningitidis in teenagers during a group B outer membrane vaccination trial in Norway. In Abstracts of the 8th International Pathogenic Neisseria Conference, pp. 895–901. Edited by C. J. Conde-Glez, S. Morse, P. Rice, F. Sparling & E. Calderon. Mexico: Insituto National de Salud Publica-Morelos-Mexico.
  96. Ross, S. C. & Densen, P. ( 1984;). Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 63, 243–273.
    [Google Scholar]
  97. Sadler, F., Fox, A., Neal, K., Dawson, M., Cartwright, K. & Borrow, R. ( 2003;). Genetic analysis of capsular status of meningococcal carrier isolates. Epidemiol Infect 130, 59–70.[CrossRef]
    [Google Scholar]
  98. Saez-Nieto, J. A., Lujan, R., Martinez-Suarez, J. V., Berron, S., Vazquez, J. A., Vinas, M. & Campos, J. ( 1990;). Neisseria lactamica and Neisseria polysaccharea as possible sources of meningococcal β-lactam resistance by genetic transformation. Antimicrob Agents Chemother 34, 2269–2272.[CrossRef]
    [Google Scholar]
  99. Sanchez, S., Troncoso, G., Ferreiros, C. M. & Criado, M. T. ( 2001;). Evaluation of cross-reactive antigens as determinants of cross-bactericidal activity in pathogenic and commensal Neisseria. Vaccine 19, 3390–3398.[CrossRef]
    [Google Scholar]
  100. Sanchez, S., Troncoso, G., Criado, M. T. & Ferreiros, C. ( 2002;). In vitro induction of memory-driven responses against Neisseria meningitidis by priming with Neisseria lactamica. Vaccine 20, 2957–2963.[CrossRef]
    [Google Scholar]
  101. Schryvers, A. B. & Stojiljkovic, I. ( 1999;). Iron acquisition systems in the pathogenic Neisseria. Mol Microbiol 32, 1117–1123.[CrossRef]
    [Google Scholar]
  102. Sim, R. J., Harrison, M. M., Moxon, E. R. & Tang, C. M. ( 2000;). Underestimation of meningococci in tonsillar tissue by nasopharyngeal swabbing. Lancet 356, 1653–1654.[CrossRef]
    [Google Scholar]
  103. Simmons, G., Jones, N. & Calder, L. ( 2000;). Equivalence of ceftriaxone and rifampicin in eliminating nasopharyngeal carriage of serogroup B Neisseria meningitidis. J Antimicrob Chemother 45, 909–911.[CrossRef]
    [Google Scholar]
  104. Simmons, G., Martin, D., Stewart, J., Jones, N., Calder, L. & Bremner, D. ( 2001;). Carriage of Neisseria meningitidis among household contacts of patients with meningococcal disease in New Zealand. Eur J Clin Microbiol Infect Dis 20, 237–242.
    [Google Scholar]
  105. Smith, H. O., Gwinn, M. L. & Salzberg, S. L. ( 1999;). DNA uptake signal sequences in naturally transformable bacteria. Res Microbiol 150, 603–616.[CrossRef]
    [Google Scholar]
  106. Snyder, L. A., Butcher, S. A. & Saunders, N. J. ( 2001;). Comparative whole-genome analyses reveal over 100 putative phase-variable genes in the pathogenic Neisseria spp. Microbiology 147, 2321–2332.
    [Google Scholar]
  107. Stefanelli, P., Fazio, C., La Rosa, G., Marianelli, C., Muscillo, M. & Mastrantonio, P. ( 2001;). Rifampicin-resistant meningococci causing invasive disease: detection of point mutations in the rpoB gene and molecular characterization of the strains. J Antimicrob Chemother 47, 219–222.[CrossRef]
    [Google Scholar]
  108. Stephens, D. S. ( 1999;). Uncloaking the meningococcus: dynamics of carriage and disease. Lancet 353, 941–942.[CrossRef]
    [Google Scholar]
  109. Stuart, J. M., Cartwright, K. A., Dawson, J. A., Rickard, J. & Noah, N. D. ( 1988;). Risk factors for meningococcal disease: a case control study in south west England. Community Med 10, 139–146.
    [Google Scholar]
  110. Stuart, J. M., Cartwright, K. A., Robinson, P. M. & Noah, N. D. ( 1989;). Effect of smoking on meningococcal carriage. Lancet 2, 723–725.
    [Google Scholar]
  111. Swartley, J. S., Marfin, A. A., Edupuganti, S., Liu, L. J., Cieslak, P., Perkins, B., Wenger, J. D. & Stephens, D. S. ( 1997;). Capsule switching of Neisseria meningitidis. Proc Natl Acad Sci U S A 94, 271–276.[CrossRef]
    [Google Scholar]
  112. Swartley, J. S., Liu, L. J., Miller, Y. K., Martin, L. E., Edupuganti, S. & Stephens, D. S. ( 1998;). Characterization of the gene cassette required for biosynthesis of the (α→6)-linked N-acetyl-d-mannosamine-1-phosphate capsule of serogroup A Neisseria meningitidis. J Bacteriol 180, 1533–1539.
    [Google Scholar]
  113. Taha, M. K., Morand, P. C., Pereira, Y., Eugene, E., Giorgini, D., Larribe, M. & Nassif, X. ( 1998;). Pilus-mediated adhesion of Neisseria meningitidis: the essential role of cell contact-dependent transcriptional upregulation of the PilC1 protein. Mol Microbiol 28, 1153–1163.[CrossRef]
    [Google Scholar]
  114. Tommassen, J., Vermeij, P., Struyve, M., Benz, R. & Poolman, J. T. ( 1990;). Isolation of Neisseria meningitidis mutants deficient in class 1 (porA) and class 3 (porB) outer membrane proteins. Infect Immun 58, 1355–1359.
    [Google Scholar]
  115. Tonjum, T., Caugant, D. A., Dunham, S. A. & Koomey, M. ( 1998;). Structure and function of repetitive sequence elements associated with a highly polymorphic domain of the Neisseria meningitidis PilQ protein. Mol Microbiol 29, 111–124.[CrossRef]
    [Google Scholar]
  116. Troncoso, G., Sanchez, S., Moreda, M., Criado, M. T. & Ferreiros, C. M. ( 2000;). Antigenic cross-reactivity between outer membrane proteins of Neisseria meningitidis and commensal Neisseria species. FEMS Immunol Med Microbiol 27, 103–109.[CrossRef]
    [Google Scholar]
  117. Troncoso, G., Sanchez, S., Kolberg, J., Rosenqvist, E., Veiga, M., Ferreiros, C. M. & Criado, M. ( 2001;). Analysis of the expression of the putatively virulence-associated neisserial protein RmpM (class 4) in commensal Neisseria and Moraxella catarrhalis strains. FEMS Microbiol Lett 199, 171–176.[CrossRef]
    [Google Scholar]
  118. Tsai, C. M., Frasch, C. E. & Mocca, L. F. ( 1981;). Five structural classes of major outer membrane proteins in Neisseria meningitidis. J Bacteriol 146, 69–78.
    [Google Scholar]
  119. Tunkel, A. R. & Scheld, W. M. ( 1993;). Pathogenesis and pathophysiology of bacterial meningitis. Clin Microbiol Rev 6, 118–136.
    [Google Scholar]
  120. Tyski, S., Grzybowska, W., Dulny, G., Berthelsen, L. & Lind, I. ( 2001;). Phenotypical and genotypical characterization of Neisseria meningitidis carrier strains isolated from Polish recruits in 1998. Eur J Clin Microbiol Infect Dis 20, 350–353.
    [Google Scholar]
  121. Tzeng, Y. L. & Stephens, D. S. ( 2000;). Epidemiology and pathogenesis of Neisseria meningitidis. Microbes Infect 2, 687–700.[CrossRef]
    [Google Scholar]
  122. 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]
  123. van der Ende, A., Hopman, C. T. & Dankert, J. ( 2000;). Multiple mechanisms of phase variation of PorA in Neisseria meningitidis. Infect Immun 68, 6685–6690.[CrossRef]
    [Google Scholar]
  124. Virji, M., Makepeace, K., Ferguson, D. J., Achtman, M. & Moxon, E. R. ( 1993;). Meningococcal Opa and Opc proteins: their role in colonization and invasion of human epithelial and endothelial cells. Mol Microbiol 10, 499–510.[CrossRef]
    [Google Scholar]
  125. Virji, M., Makepeace, K. & Moxon, E. R. ( 1994;). Distinct mechanisms of interactions of Opc-expressing meningococci at apical and basolateral surfaces of human endothelial cells; the role of integrins in apical interactions. Mol Microbiol 14, 173–184.[CrossRef]
    [Google Scholar]
  126. Vitovski, S., Read, R. C. & Sayers, J. R. ( 1999;). Invasive isolates of Neisseria meningitidis possess enhanced immunoglobulin A1 protease activity compared to colonizing strains. FASEB J 13, 331–337.
    [Google Scholar]
  127. Vogel, U., Claus, H. & Frosch, M. ( 2001;). Capsule operons. In Meningococcal Disease, Methods and Protocols, pp. 187–201. Edited by A. J. Pollard & M. C. Maiden. Totowa, NJ: Humana Press.
  128. Weichselbaum, A. ( 1887;). Über die aetiologie der akuten meningitis cerebro-spinalis. Fortschr Med 5, 573–583.
    [Google Scholar]
  129. Wilder-Smith, A., Barkham, T. M., Earnest, A. & Paton, N. I. ( 2002;). Acquisition of W135 meningococcal carriage in Hajj pilgrims and transmission to household contacts: prospective study. BMJ 325, 365–366.[CrossRef]
    [Google Scholar]
  130. Wolfgang, M., van Putten, J. P., Hayes, S. F., Dorward, D. & Koomey, M. ( 2000;). Components and dynamics of fiber formation define a ubiquitous biogenesis pathway for bacterial pili. EMBO J 19, 6408–6418.[CrossRef]
    [Google Scholar]
  131. Yagupsky, P., Ashkenazi, S. & Block, C. ( 1993;). Rifampicin-resistant meningococci causing invasive disease and failure of chemoprophylaxis. Lancet 341, 1152–1153.
    [Google Scholar]
  132. Yoshino, T., Tanaka, T., Takeyama, H. & Matsunaga, T. ( 2003;). Single nucleotide polymorphism genotyping of aldehyde dehydrogenase 2 gene using a single bacterial magnetic particle. Biosens Bioelectron 18, 661–666.[CrossRef]
    [Google Scholar]
  133. Young, L. S., LaForce, F. M., Head, J. J., Feeley, J. C. & Bennett, J. V. ( 1972;). A simultaneous outbreak of meningococcal and influenza infection. N Engl J Med 287, 5–9.[CrossRef]
    [Google Scholar]
  134. Zagursky, R. J., Olmsted, S. B., Russell, D. P. & Wooters, J. L. ( 2003;). Bioinformatics: how it is being used to identify bacterial vaccine candidates. Expert Rev Vaccines 2, 417–436.[CrossRef]
    [Google Scholar]
  135. Zhang, Q., Choo, S., Everard, J., Jennings, R. & Finn, A. ( 2000;). Mucosal immune responses to meningococcal group C conjugate and group A and C polysaccharide vaccines in adolescents. Infect Immun 68, 2692–2697.[CrossRef]
    [Google Scholar]
  136. Zhu, P., Hu, X. & Xu, L. ( 1995;). Typing Neisseria meningitidis by analysis of restriction fragment length polymorphisms in the gene encoding the class 1 outer membrane protein: application to assessment of epidemics throughout the last 4 decades in China. J Clin Microbiol 33, 458–462.
    [Google Scholar]
  137. Zhu, P., Klutch, M. J., Bash, M. C., Tsang, R. S., Ng, L. K. & Tsai, C. M. ( 2002;). Genetic diversity of three lgt loci for biosynthesis of lipooligosaccharide (LOS) in Neisseria species. Microbiology 148, 1833–1844.
    [Google Scholar]
  138. Zollinger, W. D. & Mandrell, R. E. ( 1977;). Outer-membrane protein and lipopolysaccharide serotyping of Neisseria meningitidis by inhibition of a solid-phase radioimmunoassay. Infect Immun 18, 424–433.
    [Google Scholar]
  139. Zollinger, W. D. & Mandrell, R. E. ( 1980;). Type-specific antigens of group A Neisseria meningitidis: lipopolysaccharide and heat-modifiable outer membrane proteins. Infect Immun 28, 451–458.
    [Google Scholar]
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