Review Article | Published:

Pathogenic neisseriae: surface modulation, pathogenesis and infection control

Nature Reviews Microbiology volume 7, pages 274286 (2009) | Download Citation

Abstract

Although renowned as a lethal pathogen, Neisseria meningitidis has adapted to be a commensal of the human nasopharynx. It shares extensive genetic and antigenic similarities with the urogenital pathogen Neisseria gonorrhoeae but displays a distinct lifestyle and niche preference. Together, they pose a considerable challenge for vaccine development as they modulate their surface structures with remarkable speed. Nonetheless, their host-cell attachment and invasion capacity is maintained, a property that could be exploited to combat tissue infiltration. With the primary focus on N. meningitidis, this Review examines the known mechanisms used by these pathogens for niche establishment and the challenges such mechanisms pose for infection control.

Key points

  • Neisseria meningitidis and Neisseria gonorrhoeae are human-specific pathogens and possess a range of mechanisms to achieve successful colonization of their unique niches. The bacteria are closely related genetically but have some important differences, one of which is the expression of capsule polysaccharides by most disease-causing N. meningitidis isolates but not by N. gonorrhoeae isolates.

  • Their specificity for the host is partly achieved by specific host adhesion mechanisms. As adhesins are required for the first step of colonization, they also constitute key virulence factors and have been studied extensively.

  • The Review examines several important aspects of the structures and functions of the well-known major adhesins, Opa, Opc and pili. In addition, the known target receptors are described and the potential role of receptor modulation in increasing host susceptibility to infection is considered.

  • A signature property of the pathogens is constant surface variation, which helps immune avoidance and is achieved by specific genetic mechanisms such as slipped strand mispairing and genomic recombination events, as well as bacterial responses to environmental factors. The bacterial capsule, lipopolysaccharide and surface proteins are subject to modulation.

  • Changes in the form of antigenic and phase variation of adhesins are compensated for by the presence of many mechanisms of adhesion and by conservation of adhesion function in structural variants of some proteins. The strategies of surface variation, host targeting and immune evasion, and the interplay of adhesins and surface polysaccharides are examined.

  • Constant surface variation has posed problems in developing broadly protective vaccines to combat some problematic strains of N. meningitidis and all strains of N. gonorrhoeae. In the search for new vaccine antigens, genome mining studies have identified numerous potential candidates, which include several previously unknown minor adhesins, many of which are autotransporter molecules.

  • Recent advances in the field also include a greater understanding of the mechanisms of host targeting and tissue invasion that are afforded by the major adhesins, such as the Opa proteins. In addition, few Opa variants predominate in meningococcal isolates and their receptor targeting function is largely conserved. These studies invite examination of such candidates for the development of strategies for the prevention of tissue infiltration.

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References

  1. 1.

    Meningococcal Carriage and Disease in Meningococcal Disease (ed. Cartwright, K.) 115–146 (John Wiley & Sons, Chichester, 1995).

  2. 2.

    & The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin. Microbiol. Rev. 17, 965–981 (2004). Presents recent advances in our understanding of the mechanisms of gonococcal pathogenesis in the context of the male and female human urogenital and genital tracts.

  3. 3.

    , , & Antigenic variation of gonococcal pilus involves assembly of separated silent gene segments. Proc. Natl Acad. Sci. USA 83, 2177–2181 (1986).

  4. 4.

    , , & Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell 47, 61–71 (1986).

  5. 5.

    & Phase and antigenic variation in bacteria. Clin. Microbiol. Rev. 17, 581–611 (2004). Provides an overview of the prevalence, mechanisms and importance of phase variation in bacteria.

  6. 6.

    et al. Point mutation in meningococcal porA gene associated with increased endemic disease. Lancet 337, 514–517 (1991).

  7. 7.

    et al. Additive and synergistic bactericidal activity of antibodies directed against minor outer membrane proteins of Neisseria meningitidis. Infect. Immun. 75, 5434–5442 (2007).

  8. 8.

    et al. A universal vaccine for serogroup B meningococcus. Proc. Natl Acad. Sci. USA 103, 10834–10839 (2006).

  9. 9.

    AL in Book Bergey's Manual of Systematic Bacteriology Vol. Two (ed. Garrity, G. M.) 777–798 (Springer US, 2005).

  10. 10.

    , , , & Carriage of Neisseria meningitidis and Neisseria lactamica in infants and children. J. Infect. Dis. 137, 112–121 (1978).

  11. 11.

    & Neisseria meningitidis: an overview of the carriage state. J. Med. Microbiol. 53, 821–832 (2004). Discusses meningococcal carriage in various contexts, including methodology, molecular epidemiology, genetic exchange, immune response elicited by carriage and effect of vaccination on carriage.

  12. 12.

    , & Human immunity to the meningococcus. IV. Immunogenicity of group A and group C meningococcal polysaccharides in human volunteers. J. Exp. Med. 129, 1367–1384 (1969).

  13. 13.

    Conquering the meningococcus. FEMS Microbiol. Rev. 31, 3–14 (2007). An overview of the current knowledge of meningococcal pathogenesis, epidemiology and basis of host susceptibility. It discusses new discoveries and their probable effect in the control and prevention of meningococcal disease.

  14. 14.

    et al. Complete genome sequence of Neisseria meningitidis serogroup B strain MC58. Science 287, 1809–1815 (2000).

  15. 15.

    et al. Complete DNA sequence of a serogroup A strain of Neisseria meningitidis Z2491. Nature 404, 502–506 (2000).

  16. 16.

    et al. Meningococcal genetic variation mechanisms viewed through comparative analysis of serogroup C strain FAM18. PLoS Genet. 3, e23 (2007).

  17. 17.

    et al. Comparative genomics identifies the genetic islands that distinguish Neisseria meningitidis, the agent of cerebrospinal meningitis, from other Neisseria species. Infect. Immun. 70, 7063–7072 (2002).

  18. 18.

    & Natural transformation of Neisseria gonorrhoeae: from DNA donation to homologous recombination. Mol. Microbiol. 59, 376–385 (2006). Describes recent developments in our understanding of the key steps of gonococcal transformation: DNA donation, uptake, processing and integration into the gonococcal chromosome.

  19. 19.

    , , & The relative contributions of recombination and mutation to the divergence of clones of Neisseria meningitidis. Mol. Biol. Evol. 16, 1496–1502 (1999). Describes the genetic diversities present in some bacterial populations at and below the species level and discusses approaches for defining bacterial species, especially highly mutable bacteria.

  20. 20.

    et al. The genetic basis of the phase variation repertoire of lipopolysaccharide immunotypes in Neisseria meningitidis. Microbiology 145, 3013–3021 (1999).

  21. 21.

    & Mechanisms of iron acquisition by the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae. Front. Biosi. 8, D1186–D1218 (2003).

  22. 22.

    Epidemic spread and antigenic variability of Neisseria meningitidis. Trends Microbiol. 3, 186–192 (1995).

  23. 23.

    & The repertoire of silent pilus genes in Neisseria gonorrhoeae: evidence for gene conversion. Cell 44, 107–115 (1986).

  24. 24.

    , & The opcA and ψ opcB regions in Neisseria: genes, pseudogenes, deletions, insertion elements and DNA islands. Mol. Microbiol. 33, 635–650 (1999).

  25. 25.

    et al. Identification of iron-activated and -repressed Fur-dependent genes by transcriptome analysis of Neisseria meningitidis group B. Proc. Natl Acad. Sci. USA 100, 9542–9547 (2003).

  26. 26.

    , & The frequency and rate of pilin antigenic variation in Neisseria gonorrhoeae. Mol. Microbiol. 58, 510–519 (2005).

  27. 27.

    & Bacterial internalization mediated by beta 1 chain integrins is determined by ligand affinity and receptor density. EMBO J. 12, 1887–1895 (1993).

  28. 28.

    , , & IFN-γ amplifies NFκB-dependent Neisseria meningitidis invasion of epithelial cells via specific upregulation of CEA-related cell adhesion molecule 1. Cell. Microbiol. 9, 2968–2983 (2007).

  29. 29.

    , , , & The N-domain of the human CD66a adhesion molecule is a target for Opa proteins of Neisseria meningitidis and Neisseria gonorrhoeae. Mol. Microbiol. 22, 929–939 (1996). First demonstration of the targeting of CEACAM1 by diverse Opa types of clinical isolates of N. meningitidis and N. gonorrhoeae.

  30. 30.

    , & Opacity-associated adhesin repertoire in hyperinvasive Neisseria meningitidis. Infect. Immun. 74, 5085–5094 (2006). This and subsequent studies by the authors examine Opa structural diversity in extensive collections of carriage and disease isolates of N. meningitidis.

  31. 31.

    & Current status of meningococcal group B vaccine candidates: capsular or noncapsular? Clin. Microbiol. Rev. 7, 559–575 (1994).

  32. 32.

    et al. 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 (1996).

  33. 33.

    , , , & 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 (2002).

  34. 34.

    et al. A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies. J. Exp. Med. 205, 1423–1434 (2008).

  35. 35.

    , , , & Interactions between Neisseria meningitidis and the complement system. Trends Microbiol. 15, 233–240 (2007).

  36. 36.

    & Molecular mechanisms and implications for infection of lipopolysaccharide variation in Neisseria. Mol. Microbiol. 16, 847–853 (1995).

  37. 37.

    et al. Cytidine 5′-monophospho-N-acetyl neuraminic acid and a low molecular weight factor from human blood cells induce lipopolysaccharide alteration in gonococci when conferring resistance to killing by human serum. Microb. Pathog. 5, 303–309 (1988).

  38. 38.

    , & Recognition of sialylated meningococcal lipopolysaccharide by siglecs expressed on myeloid cells leads to enhanced bacterial uptake. Mol. Microbiol 49, 1213–1225 (2003).

  39. 39.

    et al. Neisseria meningitidis lipopolysaccharides in human pathology. J. Endotoxin Res. 7, 401–420 (2001).

  40. 40.

    , & Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili. Microb. Pathog. 18, 81–96 (1995).

  41. 41.

    et al. Invasion of endothelial cells by Neisseria meningitidis requires cortactin recruitment by a phosphoinositide-3-kinase/Rac1 signalling pathway triggered by the lipo-oligosaccharide. J. Cell Sci. 118, 3805–3816 (2005).

  42. 42.

    et al. Opc- and pilus-dependent interactions of meningococci with human endothelial cells: molecular mechanisms and modulation by surface polysaccharides. Mol. Microbiol. 18, 741–754 (1995). Illustrates the interplay between several surface components of meningococci and its influence on host-cell interactions. Describes the mechanism of Opc-mediated invasion of endothelial cells.

  43. 43.

    , , & A systematic genetic analysis in Neisseria meningitidis defines the Pil proteins required for assembly, functionality, stabilization and export of type IV pili. Mol. Microbiol. 61, 1510–1522 (2006). In depth study on the molecular components that are involved in pilus assembly, functional maturation, emergence at the surface and retraction.

  44. 44.

    et al. Pilus-facilitated adherence of Neisseria meningitidis to human epithelial and endothelial cells: modulation of adherence phenotype occurs concurrently with changes in primary amino acid sequence and the glycosylation status of pilin. Mol. Microbiol. 10, 1013–1028 (1993).

  45. 45.

    et al. Structure of the fibre-forming protein pilin at 2.6 Å resolution. Nature 378, 32–38 (1995).

  46. 46.

    Post-translational modifications of meningococcal pili. Identification of common substituents: glycans and α-glycerophosphate — a review. Gene 192, 141–147 (1997). Review of the discovery of glycans and of the identification of digalactosyl 2,4-diacetamido-2,4, 6-trideoxyhexose on meningococcal pili. See reference 51 for a variant structure and reference 49 for genes involved in pilin glycosylation and frequency of variation.

  47. 47.

    et al. Type-4 pili and meningococcal adhesiveness. Gene 192, 149–153 (1997).

  48. 48.

    & Role of glycosylation at Ser63 in production of soluble pilin in pathogenic Neisseria. J. Bacteriol. 181, 656–661 (1999).

  49. 49.

    et al. Genetic characterization of pilin glycosylation and phase variation in Neisseria meningitidis. Mol. Microbiol. 49, 833–847 (2003).

  50. 50.

    & The role of pilin glycan in neisserial pathogenesis. Mol. Cell. Biochem. 253, 179–190 (2003).

  51. 51.

    et al. Alternative Neisseria spp. type IV pilin glycosylation with a glyceramido acetamido trideoxyhexose residue. Proc. Natl Acad. Sci. USA 104, 14783–14788 (2007).

  52. 52.

    et al. Unique modifications with phosphocholine and phosphoethanolamine define alternate antigenic forms of Neisseria gonorrhoeae type IV pili. Proc. Natl Acad. Sci. USA 101, 10798–10803 (2004).

  53. 53.

    , , , & The phosphorylcholine epitope undergoes phase variation on a 43-kilodalton protein in Pseudomonas aeruginosa and on pili of Neisseria meningitidis and Neisseria gonorrhoeae. Infect. Immun. 66, 4263–4267 (1998).

  54. 54.

    , , , & Bacterial phosphorylcholine decreases susceptibility to the antimicrobial peptide LL-37/hCAP18 expressed in the upper respiratory tract. Infect. Immun. 68, 1664–1671 (2000).

  55. 55.

    & Genetic and functional analysis of the phosphorylcholine moiety of commensal Neisseria lipopolysaccharide. Mol. Microbiol. 43, 437–448 (2002).

  56. 56.

    , & Decoration of lipopolysaccharide with phosphorylcholine: a phase-variable characteristic of Haemophilus influenzae. Infect. Immun. 65, 943–950 (1997).

  57. 57.

    et al. Genetic and functional analyses of PptA, a phospho-form transferase targeting type IV pili in Neisseria gonorrhoeae. J. Bacteriol. 190, 387–400 (2008).

  58. 58.

    & Identification and characterization of pptA: a gene involved in the phase-variable expression of phosphorylcholine on pili of Neisseria meningitidis. Infect. Immun. 71, 6892–6898 (2003).

  59. 59.

    et al. Type IV pilus structure by cryo–electron microscopy and crystallography: implications for pilus assembly and functions. Mol. Cell 23, 651–662 (2006).

  60. 60.

    et al. Efficacy trial of a parenteral gonococcal pilus vaccine in men. Vaccine 9, 154–162 (1991).

  61. 61.

    , , , & 3D structure/function analysis of PilX reveals how minor pilins can modulate the virulence properties of type IV pili. Proc. Natl Acad. Sci. USA 104, 15888–15893 (2007).

  62. 62.

    , , , & Transformation competence and type-4 pilus biogenesis in Neisseria gonorrhoeae — a review. Gene 192, 125–134 (1997).

  63. 63.

    et al. A conserved set of pilin-like molecules controls type IV pilus dynamics and organelle-associated functions in Neisseria gonorrhoeae. Mol. Microbiol. 56, 903–917 (2005).

  64. 64.

    , & Pilus retraction powers bacterial twitching motility. Nature 407, 98–102 (2000).

  65. 65.

    et al. Single pilus motor forces exceed 100 pN. Proc. Natl Acad. Sci. USA 99, 16012–16017 (2002). References 64 and 65 demonstrate that N. gonorrhoeae pili retract with a force that can exceed 80 picoNewton. The studies provide the evidence that single retraction events are powered by the action of a single PilT complex on a single pilus fibre.

  66. 66.

    Studies on gonococcus infection. XIV. Cell wall protein differences among color/opacity colony variants of Neisseria gonorrhoeae. Infect. Immun. 21, 292–302 (1978).

  67. 67.

    et al. Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis. Mol. Microbiol. 6, 2785–2795 (1992).

  68. 68.

    et al. Recombinational reassortment among opa genes from ET-37 complex Neisseria meningitidis isolates of diverse geographical origins. Microbiology 144, 157–166 (1998).

  69. 69.

    , , & Specificity of bactericidal antibody response to serogroup B meningococcal strains in Brazilian children after immunization with an outer membrane vaccine. Infect. Immun. 66, 4755–4761 (1998).

  70. 70.

    et al. Functional activity of antibodies against the recombinant OpaJ protein from Neisseria meningitidis. Infect. Immun. 71, 2331–2340 (2003).

  71. 71.

    , , , & Allelic polymorphism and site-specific recombination in the opc locus of Neisseria meningitidis. Mol. Microbiol. 19, 841–856 (1996).

  72. 72.

    et al. Fibronectin mediates Opc-dependent internalization of Neisseria meningitidis in human brain microvascular endothelial cells. Mol. Microbiol. 46, 933–946 (2002).

  73. 73.

    , , & The changing epidemiology of invasive meningococcal disease in Canada, 1985 through 1992. Emergence of a virulent clone of Neisseria meningitidis. JAMA 273, 390–394 (1995).

  74. 74.

    , & Targeted vaccination with meningococcal polysaccharide vaccine in one district of the Czech Republic. Epidemiol. Infect. 115, 411–418 (1995).

  75. 75.

    , , , & Identification and characterisation of a novel conserved outer membrane protein from Neisseria meningitidis. FEMS Immunol. Med. Microbiol. 28, 329–334 (2000).

  76. 76.

    et al. Neisseria meningitidis NhhA is a multifunctional trimeric autotransporter adhesin. Mol. Microbiol. 61, 631–644 (2006).

  77. 77.

    et al. Neisseria meningitidis App, a new adhesin with autocatalytic serine protease activity. Mol. Microbiol. 48, 323–334 (2003).

  78. 78.

    et al. A functional two-partner secretion system contributes to adhesion of Neisseria meningitidis to epithelial cells. J. Bacteriol. 189, 7968–7976 (2007).

  79. 79.

    et al. NadA, a novel vaccine candidate of Neisseria meningitidis. J. Exp. Med. 195, 1445–1454 (2002).

  80. 80.

    et al. NadA diversity and carriage in Neisseria meningitidis. Infect. Immun. 72, 4217–4223 (2004).

  81. 81.

    et al. Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA. Vaccine 26, 4244–4250 (2008).

  82. 82.

    et al. Characterization of MspA, an immunogenic autotransporter protein that mediates adhesion to epithelial and endothelial cells in Neisseria meningitidis. Infect. Immun. 74, 2957–2964 (2006).

  83. 83.

    , , , & Meningococcal Opa and Opc proteins — their role in colonization and invasion of human epithelial and endothelial-cells. Mol. Microbiol. 10, 499–510 (1993).

  84. 84.

    , , & The influence of surface charge on the attachment of Neisseria gonorrhoeae to human cells. J. Gen. Microbiol. 96, 359–364 (1976).

  85. 85.

    , & Evidence for functionally distinct pili expressed by Neisseria meningitidis. Infect. Immun. 59, 3169–3175 (1991).

  86. 86.

    , , , & Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue. Mol. Microbiol. 13, 403–416 (1994).

  87. 87.

    & The PilC adhesin of the Neisseria type IV pilus-binding specificities and new insights into the nature of the host cell receptor. Mol. Microbiol. 56, 945–957 (2005).

  88. 88.

    , , & Interactions of Neisseria meningitidis with cells of the human meninges. Mol. Microbiol. 36, 817–829 (2000).

  89. 89.

    , , , & Roles of PilC and PilE proteins in pilus-mediated adherence of Neisseria gonorrhoeae and Neisseria meningitidis to human erythrocytes and endothelial and epithelial cells. Infect. Immun. 67, 834–843 (1999).

  90. 90.

    et al. Attachment of Neisseria gonorrhoeae to the cellular pilus receptor CD46: identification of domains important for bacterial adherence. Cell. Microbiol. 3, 133–143 (2001).

  91. 91.

    & Inverse relationship between pilus-mediated gonococcal adherence and surface expression of the pilus receptor, CD46. Microbiology 147, 2333–2340 (2001).

  92. 92.

    et al. A novel interaction between type IV pili of Neisseria gonorrhoeae and the human complement regulator C4B-binding protein. J. Immunol. 166, 6764–6770 (2001).

  93. 93.

    , , & Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan sulfate. J. Exp. Med. 182, 511–517 (1995).

  94. 94.

    et al. Recognition of saccharides by the OpcA, OpaD, and OpaB outer membrane proteins from Neisseria meningitidis. J. Biol. Chem. 280, 31489–31497 (2005).

  95. 95.

    & Binding of syndecan-like cell surface proteoglycan receptors is required for Neisseria gonorrhoeae entry into human mucosal cells. EMBO J. 14, 2144–2154 (1995).

  96. 96.

    et al. Critical determinants of host receptor targeting by Neisseria meningitidis and Neisseria gonorrhoeae: identification of Opa adhesiotopes on the N-domain of CD66 molecules. Mol. Microbiol. 34, 538–551 (1999).

  97. 97.

    , , , & Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors. Mol. Microbiol. 27, 1203–1212 (1998).

  98. 98.

    , & Crystal structure of the OpcA integral membrane adhesin from Neisseria meningitidis. Proc. Natl Acad. Sci. USA 99, 3417–3421 (2002).

  99. 99.

    , & 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 (1994).

  100. 100.

    & Vitronectin binds to the gonococcal adhesin OpaA through a glycosaminoglycan molecular bridge. Biochem. J. 334 133–139 (1998).

  101. 101.

    The carcinoembryonic antigen (CEA) family: structures, suggested functions and expression in normal and malignant tissues. Semin. Cancer Biol. 9, 67–81 (1999).

  102. 102.

    et al. Carcinoembryonic antigen family receptor specificity of Neisseria meningitidis Opa variants influences adherence to and invasion of proinflammatory cytokine-activated endothelial cells. Infect. Immun. 68, 3601–3607 (2000).

  103. 103.

    & CGM1a antigen of neutrophils, a receptor of gonococcal opacity proteins. Proc. Natl Acad. Sci. USA 93, 14851–14856 (1996).

  104. 104.

    , & The immune response in adenoids and tonsils. Int. Arch. Allergy Immunol. 122, 8–19 (2000).

  105. 105.

    , , & Host genetic determinants of Neisseria meningitidis infections. Lancet Infect. Dis. 3, 565–577 (2003).

  106. 106.

    , , & Respiratory viral infection predisposing for bacterial disease: a concise review. FEMS Immunol. Med. Microbiol. 26, 189–195 (1999).

  107. 107.

    et al. Interferon-γ tempers the expression of carcinoembryonic antigen family molecules in human colon cells: a possible role in innate mucosal defence. Scand. J. Immunol. 58, 628–641 (2003).

  108. 108.

    & Is there a role for CEA in innate immunity in the colon? Trends Microbiol. 9, 119–125 (2001).

  109. 109.

    & A novel cell-binding mechanism of Moraxella catarrhalis ubiquitous surface protein UspA: specific targeting of the N-domain of carcinoembryonic antigen-related cell adhesion molecules by UspA1. Mol. Microbiol. 48, 117–129 (2003).

  110. 110.

    et al. The variable P5 proteins of typeable and non-typeable Haemophilus influenzae target human CEACAM1. Mol. Microbiol. 39, 850–862 (2001).

  111. 111.

    , , & Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)-binding recombinant polypeptide confers protection against infection by respiratory and urogenital pathogens. Mol. Microbiol. 55, 1515–1527 (2005). Together with reference 30, this study provides a case for the protective role of certain receptor-blocking strategies to prevent infection by mucosal pathogens.

  112. 112.

    et al. The Moraxella adhesin UspA1 binds to its human CEACAM1 receptor by a deformable trimeric coiled-coil. EMBO J. 27, 1779–1789 (2008).

  113. 113.

    , , , & Molecular surveillance of Neisseria meningitidis capsular switching in Portugal, 2002–2006. Epidemiol. Infect. 137, 161–165 (2008).

  114. 114.

    , , , & Herd immunity from meningococcal serogroup C conjugate vaccination in England: database analysis. BMJ 326, 365–366 (2003).

  115. 115.

    Carbohydrates as future anti-adhesion drugs for infectious diseases. Biochim. Biophys. Acta 1760, 527–537 (2006).

  116. 116.

    & Protein secretion and secreted proteins in pathogenic Neisseriaceae. FEMS Microbiol. Rev. 30, 292–319 (2006).

  117. 117.

    , , & Neisserial PorB is translocated to the mitochondria of HeLa cells infected with Neisseria meningitidis and protects cells from apoptosis. Cell. Microbiol. 5, 99–109 (2003).

  118. 118.

    , & Gonococcal invasion of epithelial cells driven by P.IA, a bacterial ion channel with GTP binding properties. J. Exp. Med. 188, 941–952 (1998).

  119. 119.

    et al. The pilus and porin of Neisseria gonorrhoeae cooperatively induce Ca2+ transients in infected epithelial cells. Cell. Microbiol. 7, 1736–1748 (2005).

  120. 120.

    , , , & Mechanism of action of blocking immunoglobulin G for Neisseria gonorrhoeae. J. Clin. Invest. 76, 1765–1772 (1985).

  121. 121.

    et al. Functional activities and epitope specificity of human and murine antibodies against the class 4 outer membrane protein (Rmp) of Neisseria meningitidis 1. Infect. Immun. 67, 1267–1276 (1999).

  122. 122.

    , & CEACAM1 dynamics during Neisseria gonorrhoeae suppression of CD4+ T lymphocyte activation. J. Immunol. 180, 6827–6835 (2008).

  123. 123.

    et al. Factor H binding and function in sialylated pathogenic Neisseriae is influenced by gonococcal, but not meningococcal, porin. J. Immunol. 178, 4489–4497 (2007).

  124. 124.

    Interactions between encapsulated Neisseria meningitidis and host cells. Int. Microbiol. 2, 133–136 (1999).

  125. 125.

    , , & Crystal structure of Neisserial surface protein A (NspA), a conserved outer membrane protein with vaccine potential. J. Biol. Chem. 278, 24825–24830 (2003).

  126. 126.

    et al. The HrpB–HrpA two-partner secretion system is essential for intracellular survival of Neisseria meningitidis. Cell. Microbiol. 10, 2461–2482 (2008).

  127. 127.

    , , & Neisseria meningitidis Opc invasin binds to the cytoskeletal protein alpha-actinin. Cell. Microbiol. 11, 389–405 (2009).

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Acknowledgements

Research in my laboratory cited here has been funded by the Wellcome Trust, the Medical Research Council, the Meningitis Research Foundation, Meningitis UK and GlaxoSmithKline. I acknowledge my colleagues D. Hill and N. Griffiths for their dedicated participation and my collaborators S. Ram, A. Hadfield, R. Sessions, J. Derrick, L. Brady and D. Ferguson for unpublished data and images included in this Review. I also thank the anonymous referees for their comments.

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  1. Department of Cellular and Molecular Medicine, School of Medical Sciences, University Walk, University of Bristol, Bristol, BS8 1TD, UK.  M.Virji@bristol.ac.uk

    • Mumtaz Virji

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The author declares no competing financial interests.

Glossary

Commensal bacterium

A bacterium that inhabits a host without apparent adverse effects to the host.

Natural competence

An innate ability of bacteria to acquire DNA from the local environment and to assimilate genetic information through homologous recombination.

Multilocus sequence typing

A technique used to characterize strains by their unique allelic profiles of a set of housekeeping genes.

Phase variation

Reversible switching on and off of surface antigens that helps bacterial evasion of host immune responses.

Anti-opsonic

A term applied to agents that prevent the binding of opsonins (for example, antibodies) that enhance phagocytosis.

Serogroup

A designation denoting the immunochemistry (structure) of the capsule polysaccharides of Neisseria meningitidis; N. meningitidis strains are divided into serogroups based on the reactivity of strains with antibodies against distinct capsule structures.

Meninges

Membranes that envelop the central nervous system.

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