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Microbiology and pathobiology of Neisseria meningitidis

Michael Apicella, MD
Section Editors
Stephen B Calderwood, MD
Sheldon L Kaplan, MD
Deputy Editor
Elinor L Baron, MD, DTMH


Infection with Neisseria meningitidis can produce a variety of clinical manifestations, ranging from transient fever and bacteremia to fulminant disease with death ensuing within hours of the onset of clinical symptoms. N. meningitidis is a common cause of community-acquired bacterial meningitis in both children and adults. (See "Bacterial meningitis in children older than one month: Clinical features and diagnosis", section on 'Causative organisms' and "Epidemiology of bacterial meningitis in adults", section on 'Community-acquired meningitis'.)

Mortality can be very high in patients with meningococcal disease if the infection is not treated appropriately, and long-term sequelae can be severe even in successfully managed cases due primarily to difficulty in managing the endotoxin-induced vascular collapse frequently induced by this organism. (See "Treatment and prevention of meningococcal infection", section on 'Prognosis'.)

The microbiology and pathobiology of N. meningitidis will be reviewed here. The epidemiology, clinical features, diagnosis, treatment, and prevention of meningococcal infections are discussed separately. (See "Epidemiology of Neisseria meningitidis infection" and "Clinical manifestations of meningococcal infection" and "Diagnosis of meningococcal infection" and "Treatment and prevention of meningococcal infection" and "Meningococcal vaccines".)


Meningococcal disease was first described in 1805 after an epidemic of meningitis in Geneva. It was not until 1882 that the pathogen responsible for this disease was first isolated from the cerebrospinal fluid of an infected patient. The fact that the organism could be carried in the nasopharynx of healthy individuals was first recognized in 1890. In 1909, immunologically distinct serotypes of the meningococcus were identified. This established the basis for serum therapy, which was instituted by Flexner in 1913 [1].

Meningococcal epidemics among military recruits were a major consequence of military mobilization. As a result, the military participated in a number of important studies dealing with meningococcal disease, including the development of chemoprophylactic and immunologic methods to prevent infection. During World War I, the British army recognized that the frequency of carriage of the case strain rose prior to and during epidemics. With the advent of sulfonamides as an early antimicrobial treatment for meningococcal disease, the United States army used chemoprophylaxis with sulfonamides to dramatically reduce the incidence of disease among recruits during World War II. After the war, the availability of penicillin G greatly improved the treatment of meningococcal meningitis and sepsis, resulting in a substantial drop in mortality rates.

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Literature review current through: Nov 2017. | This topic last updated: Oct 19, 2017.
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  2. Artenstein MS, Gold R, Zimmerly JG, et al. Prevention of meningococcal disease by group C polysaccharide vaccine. N Engl J Med 1970; 282:417.
  3. Sun YH, Bakshi S, Chalmers R, Tang CM. Functional genomics of Neisseria meningitidis pathogenesis. Nat Med 2000; 6:1269.
  4. Newcombe J, Cartwright K, Palmer WH, McFadden J. PCR of peripheral blood for diagnosis of meningococcal disease. J Clin Microbiol 1996; 34:1637.
  5. Yazdankhah SP, Caugant DA. Neisseria meningitidis: an overview of the carriage state. J Med Microbiol 2004; 53:821.
  6. Rosenstein NE, Perkins BA, Stephens DS, et al. Meningococcal disease. N Engl J Med 2001; 344:1378.
  7. Rudel T, Boxberger HJ, Meyer TF. Pilus biogenesis and epithelial cell adherence of Neisseria gonorrhoeae pilC double knock-out mutants. Mol Microbiol 1995; 17:1057.
  8. Virji M, Makepeace K, Peak I, et al. Functional implications of the expression of PilC proteins in meningococci. Mol Microbiol 1995; 16:1087.
  9. Rudel T, Scheurerpflug I, Meyer TF. Neisseria PilC protein identified as type-4 pilus tip-located adhesin. Nature 1995; 373:357.
  10. Scheuerpflug I, Rudel T, Ryll R, et al. 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 1999; 67:834.
  11. Power PM, Roddam LF, Rutter K, et al. Genetic characterization of pilin glycosylation and phase variation in Neisseria meningitidis. Mol Microbiol 2003; 49:833.
  12. Warren MJ, Jennings MP. Identification and characterization of pptA: a gene involved in the phase-variable expression of phosphorylcholine on pili of Neisseria meningitidis. Infect Immun 2003; 71:6892.
  13. Chamot-Rooke J, Mikaty G, Malosse C, et al. Posttranslational modification of pili upon cell contact triggers N. meningitidis dissemination. Science 2011; 331:778.
  14. Jen FE, Warren MJ, Schulz BL, et al. Dual pili post-translational modifications synergize to mediate meningococcal adherence to platelet activating factor receptor on human airway cells. PLoS Pathog 2013; 9:e1003377.
  15. Källström H, Liszewski MK, Atkinson JP, Jonsson AB. Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol Microbiol 1997; 25:639.
  16. Källström H, Islam MS, Berggren PO, Jonsson AB. Cell signaling by the type IV pili of pathogenic Neisseria. J Biol Chem 1998; 273:21777.
  17. Merz AJ, So M. Attachment of piliated, Opa- and Opc- gonococci and meningococci to epithelial cells elicits cortical actin rearrangements and clustering of tyrosine-phosphorylated proteins. Infect Immun 1997; 65:4341.
  18. de Vries FP, van Der Ende A, van Putten JP, Dankert J. Invasion of primary nasopharyngeal epithelial cells by Neisseria meningitidis is controlled by phase variation of multiple surface antigens. Infect Immun 1996; 64:2998.
  19. Callaghan MJ, Jolley KA, Maiden MC. Opacity-associated adhesin repertoire in hyperinvasive Neisseria meningitidis. Infect Immun 2006; 74:5085.
  20. Virji M, Makepeace K, Ferguson DJ, et al. Meningococcal Opa and Opc proteins: their role in colonization and invasion of human epithelial and endothelial cells. Mol Microbiol 1993; 10:499.
  21. de Vries FP, Cole R, Dankert J, et al. Neisseria meningitidis producing the Opc adhesin binds epithelial cell proteoglycan receptors. Mol Microbiol 1998; 27:1203.
  22. Kahler CM, Stephens DS. Genetic basis for biosynthesis, structure, and function of meningococcal lipooligosaccharide (endotoxin). Crit Rev Microbiol 1998; 24:281.
  23. Mandrell RE, Apicella MA. Lipo-oligosaccharides (LOS) of mucosal pathogens: molecular mimicry and host-modification of LOS. Immunobiology 1993; 187:382.
  24. Persa OD, Jazmati N, Robinson N, et al. A pregnant woman with chronic meningococcaemia from Neisseria meningitidis with lpxL1-mutations. Lancet 2014; 384:1900.
  25. Mandrell RE, Zollinger WD. Lipopolysaccharide serotyping of Neisseria meningitidis by hemagglutination inhibition. Infect Immun 1977; 16:471.
  26. Kulshin VA, Zähringer U, Lindner B, et al. Structural characterization of the lipid A component of pathogenic Neisseria meningitidis. J Bacteriol 1992; 174:1793.
  27. Fransen F, Heckenberg SG, Hamstra HJ, et al. Naturally occurring lipid A mutants in neisseria meningitidis from patients with invasive meningococcal disease are associated with reduced coagulopathy. PLoS Pathog 2009; 5:e1000396.
  28. Cesarini JP, Vandekerkove M, Faucon R, Nicoli J. [Ultrastructure of the wall of Neisseria meningitidis]. Ann Inst Pasteur (Paris) 1967; 113:833.
  29. Kroll JS, Moxon ER. Capsulation and gene copy number at the cap locus of Haemophilus influenzae type b. J Bacteriol 1988; 170:859.
  30. Finne J, Leinonen M, Mäkelä PH. Antigenic similarities between brain components and bacteria causing meningitis. Implications for vaccine development and pathogenesis. Lancet 1983; 2:355.
  31. Deghmane AE, Giorgini D, Larribe M, et al. Down-regulation of pili and capsule of Neisseria meningitidis upon contact with epithelial cells is mediated by CrgA regulatory protein. Mol Microbiol 2002; 43:1555.
  32. Hammerschmidt S, Hilse R, van Putten JP, et al. Modulation of cell surface sialic acid expression in Neisseria meningitidis via a transposable genetic element. EMBO J 1996; 15:192.
  33. Spinosa MR, Progida C, Talà A, et al. The Neisseria meningitidis capsule is important for intracellular survival in human cells. Infect Immun 2007; 75:3594.
  34. Harrison LH, Shutt KA, Schmink SE, et al. Population structure and capsular switching of invasive Neisseria meningitidis isolates in the pre-meningococcal conjugate vaccine era--United States, 2000-2005. J Infect Dis 2010; 201:1208.
  35. Seib KL, Scarselli M, Comanducci M, et al. Neisseria meningitidis factor H-binding protein fHbp: a key virulence factor and vaccine antigen. Expert Rev Vaccines 2015; 14:841.
  36. McNeil LK, Zagursky RJ, Lin SL, et al. Role of factor H binding protein in Neisseria meningitidis virulence and its potential as a vaccine candidate to broadly protect against meningococcal disease. Microbiol Mol Biol Rev 2013; 77:234.
  37. Hammerschmidt S, Müller A, Sillmann H, 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 1996; 20:1211.
  38. Lin L, Ayala P, Larson J, et al. The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells. Mol Microbiol 1997; 24:1083.
  39. McNeil G, Virji M. Phenotypic variants of meningococci and their potential in phagocytic interactions: the influence of opacity proteins, pili, PilC and surface sialic acids. Microb Pathog 1997; 22:295.
  40. Kahler CM, Martin LE, Shih GC, et al. The (alpha2-->8)-linked polysialic acid capsule and lipooligosaccharide structure both contribute to the ability of serogroup B Neisseria meningitidis to resist the bactericidal activity of normal human serum. Infect Immun 1998; 66:5939.
  41. Estabrook MM, Zhou D, Apicella MA. Nonopsonic phagocytosis of group C Neisseria meningitidis by human neutrophils. Infect Immun 1998; 66:1028.
  42. Jack DL, Dodds AW, Anwar N, et al. Activation of complement by mannose-binding lectin on isogenic mutants of Neisseria meningitidis serogroup B. J Immunol 1998; 160:1346.
  43. Sprong T, Mollnes TE, Neeleman C, et al. Mannose-binding lectin is a critical factor in systemic complement activation during meningococcal septic shock. Clin Infect Dis 2009; 49:1380.
  44. Granoff DM, Welsch JA, Ram S. Binding of complement factor H (fH) to Neisseria meningitidis is specific for human fH and inhibits complement activation by rat and rabbit sera. Infect Immun 2009; 77:764.
  45. Madico G, Welsch JA, Lewis LA, et al. The meningococcal vaccine candidate GNA1870 binds the complement regulatory protein factor H and enhances serum resistance. J Immunol 2006; 177:501.
  46. Welsch JA, Ram S, Koeberling O, Granoff DM. Complement-dependent synergistic bactericidal activity of antibodies against factor H-binding protein, a sparsely distributed meningococcal vaccine antigen. J Infect Dis 2008; 197:1053.
  47. Beernink PT, Leipus A, Granoff DM. Rapid genetic grouping of factor h-binding protein (genome-derived neisserial antigen 1870), a promising group B meningococcal vaccine candidate. Clin Vaccine Immunol 2006; 13:758.
  48. Lappann M, Haagensen JA, Claus H, et al. Meningococcal biofilm formation: structure, development and phenotypes in a standardized continuous flow system. Mol Microbiol 2006; 62:1292.