Skip to main content

Studies on the Molecular Mechanisms of Meningococcal Interactions with Human Cells

Towards Anti-Adhesion Measures for the Control of Meningococcal Disease

  • Chapter
Book cover Toward Anti-Adhesion Therapy for Microbial Diseases

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 408))

Abstract

The meningitis-causing organism, Neisseria meningitidis, is a human pathogen with exquisite affinity for the nasopharyngeal tissue of its host where it may exist as a harmless commensal in up to 30% of healthy individuals (DeVoe, 1982). However, in some cases, predisposing factors which are poorly understood, make the host susceptible to further invasion by these bacteria. In such cases, meningococci breach the epithelial barrier of the nasopharynx and disseminate throughout the body via the blood stream. Blood stream invasion is often associated with endothelial necrosis and intra-vascular coagulation which result in skin lesions common in disseminated meningococcal infections. Further tissue infiltration including that of the central nervous system may ensue in untreated cases, with serious outcomes including death. Factors that are implicated in bacterial virulence include polymeric proteins, pili, which are composed of repeating subunits (pilins). Pili extend beyond the capsule which is invariably present on the surface of bacteria isolated from blood or cerebrospinal fluid (csf) (DeVoe and Gilchrist, 1975). Two structural classes of pili occur in N. meningitidis. Class I pili are similar to gonococcal pili whereas Class II pili produce pilins of smaller Mr (Diaz et al, 1984, Perry et al., 1988, Virji et al., 1989). Both classes of pili occur in clinical isolates but are mutually exclusive within a given strain. Pili undergo phase and antigenic variation as a result of inter- and intra-genomic recombinational events (reviewed Saunders et al., 1994). In addition, two outer membrane proteins, Opa and Opc, may also increase the potential of meningococci to interact with human cells. These proteins are classified as Class 5 proteins or opacity proteins (since they impart opacity to colonies of bacteria expressing the proteins). Opa proteins are a family of antigenically variable proteins and occur in N. meningitidis as well as in the closely related organism N. gonorrhoeae (Cannon, 1994). In meningococci, 3–4 opa gene loci code for related proteins with conserved, semivariable and hypervariable domains. Opc protein is largely invariant and is expressed in all epidemic and highly pathogenic strains other than ET37 complex of serogroup C meningococci and gonococci (Olyhoek et al., 1991, Wang et al., 1993).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Cannon, J.G. (1994) In Neisseria 94. Genetics and function of Opa proteins: Progress and unanswered questions. Proceedings of the Ninth International Pathogenic Neisseria Conference, pp. 70–72. Editors J.S. Evans, S.E. Yost, M.C.J. Maiden and I.M. Feavers.

    Google Scholar 

  2. Cartwright, K.A.V., Stuart, J.M., Jones, D.M. and Noah, N.D. (1987) The Stonehouse survey: nasopharyngeal carriage of meningococcal and Neisseria lactamica. Epidem Inf 99: 591–601.

    Article  CAS  Google Scholar 

  3. Castric, P. (1995) PilO, a gene required for glycosylation of Pseudomonas aeruginosa 1244 pilin. Microbiology 141: 1247–1254.

    Article  PubMed  CAS  Google Scholar 

  4. DeVoe, I.W. (1982) The Meningococcus and Mechanisms of Pathogenicity. Microb Reviews 46: 162–190.

    Google Scholar 

  5. DeVoe, I.W., and Gilchrist, J.E. (1975) Pili on meningococci from primary cultures of nasopharyngeal carriers and cerebrospinal fluid of patients with acute disease. J Exp Med 141: 297–305.

    Article  Google Scholar 

  6. Diaz, J.–L., Virji, M. & Heckels, J.E. (1984). Structural and antigenic differences between two types of meningococcal pili. FEMS Microb Lett 21, 181–184.

    Article  Google Scholar 

  7. Dunn, K.L.R., Virji, M. and Moxon, E.R. (1995) Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili. Microb Pathogen 18: 81–96.

    Article  CAS  Google Scholar 

  8. Garbe, T., Harris, D., Vordermeier, M., Lathigra, R., Ivanyi, J. and Young, D. (1993) Expression of the Mycobacterium tuberculosis 19-kilodalton antigen in Mycobacterium smegmatis - immunological analysis and evidence of glycosylation. Infect Immun 61: 260–267.

    PubMed  CAS  Google Scholar 

  9. Jonsson, A.-B., Nyberg, G. and Normark, S. (1991) Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J 10: 477–488.

    PubMed  CAS  Google Scholar 

  10. Jonsson, A. -B., Iver, D., Falk. P., Pepose, J. and Normark, S. (1994) Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue. Mol Microbiol 13: 403–416.

    Article  PubMed  CAS  Google Scholar 

  11. McNeil, G., Virji, M. and Moxon, E.R. (1994a) Interactions of Neisseria meningitidis with human monocytes. Microb Pathogen 16, 153–163.

    Article  CAS  Google Scholar 

  12. McNeil, G., Virji, M. and Moxon, E.R. (1994b). Interactions of Neisseria meningitidis expressing Opc and Opa proteins with human phagocytes. In Neisseria 94. Proceedings of the Ninth International Pathogenic Neisseria Conference, pp. 265–267. Editors J.S. Evans, S.E. Yost, M.C.J. Maiden and I.M. Feavers.

    Google Scholar 

  13. McNeil, G. and Virji, M. (1996). Phenotypic variants of meningococci and their potential in phagocytic interactions: the influence of opacity proteins, pili, PilC and surface sialic acids (submitted to Microb Pathogen).

    Google Scholar 

  14. Nassif, X., Lowry, J. Stenberg, P., O’Gaora, P., Ganji, A. and So, M. (1993) Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells. Mol Microbiol 8: 719–725.

    Article  PubMed  CAS  Google Scholar 

  15. Nassif, X., Beretti, J-L., Lowy, J., Stenberg, P., O’Gaora, P., Pfeifer, J., Normark, S., and So, M. (1994) Roles of pilin and PilC in adhesion of Neisseria meningitidis to human epithelial and endothelial cells. Proc Nat Acad Sci USA 91: 3769–3773.

    Article  PubMed  CAS  Google Scholar 

  16. Olyhoek, A.J.M., Sarkari, J., Bopp, M., Morelli, G. and Achtman, M. (1991) Cloning and expression in Escherichia coli of opc, the gene for an unusual Class 5 outer membrane protein from Neisseria meningitidis. Microb Pathogen 11: 249–257.

    Article  CAS  Google Scholar 

  17. Perry, A.C.F., Nicolson, I.J. and Saunders, J.R. (1988) Neisseria meningitidis CI 14 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeaepil sequences J Bacteriol 170: 1691–1697.

    CAS  Google Scholar 

  18. Rudel, T., van Putten, J.P.M., Gibbs, C.P., Haas, R. and Meyer, T.F. (1992) Interaction of two variable proteins (pilE and pilC) required for pilus-mediated adherence of Neisseria gonorrhoeae to human epithelial cells. Mol Microbiol 6: 3439–3450.

    Article  PubMed  CAS  Google Scholar 

  19. Ruoslahti, E., and Pierschbacher, M.D. (1987) New Perspectives in Cell Adhesion: RGD and Integrins. Science 238: 491–497.

    Article  PubMed  CAS  Google Scholar 

  20. Saunders, J.R., O’Sullivan, H., Wakeman, J., Sims, G., Hart, C.A., Virji, M., Heckels, J.E., Winstanley, C., Morgan, J.A.W. & Pickup, R.W. (1994) Flagella and pili as antigenically variable structures on the bacterial surface. In Microbial Cell Envelopes: Interactions and Biofilms, pp. 33–42, Edited by L.B. Quesnel, P. Gilbert and P.S. Handley, Blackwell Scientific Publications.

    Google Scholar 

  21. Sharon, N. and Jeanloz, R.W. (1960) The diaminohexose component of a polysaccharide isolated from Bacillus subtilis. J Biol Chem 235: 1–5.

    PubMed  CAS  Google Scholar 

  22. Stephens, D.S. (1989) Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture and organ culture assays. Clin Microbiol Rev 2: S104-S111.

    PubMed  Google Scholar 

  23. Stimson, E., Virji, M., Makepeace, K., Dell, A., Morris, H. R., Payne, G., Saunders, J. R., Jennings, M. P., Barker, S., Panico, M., Blench, I. and Moxon, E. R. (1995) Meningococcal pilin: a glycoprotein substituted with digalactosyl 2,4-diacetamido-2,4,6-trideoxyhexose. Mol Microbiol 17(6): 1201–1214.

    Article  PubMed  CAS  Google Scholar 

  24. Stimson, E., Virji, M., Barker, S., Panico, M., Blench, I. Saunders, J.R., Payne, G., Moxon, E.R., Dell, A. and Morris, H.R. (1996) Discovery of a novel protein modification: a-glycerophosphate is a substituent of meningococcal pilin. (Biochem J. in press)

    Google Scholar 

  25. Trust, T. J., Gillespie, R. M., Bhatti, A. R. and White, L. A. (1983) Differences in the adhesive properties of Neissseria meningitidis for human buccal epithilial cells and erythrocytes. Infect Immun 41:106–113.

    PubMed  CAS  Google Scholar 

  26. Viiji, M., Heckels, J. E., Potts, W. J., Hart, C. A. and Saunders, J. R. (1989). Identification of the epitopes recognised by monoclonal antibodies SMI and SM2 which react with all pili of Neisseria gonorrhoeae but which differentiate between two structural classes of pili expressed by Neisseria meningitidis and the distribution of their encoding sequences in the genomes of Neisseria spp. J Gen Microbiol 135: 3239–3251.

    Google Scholar 

  27. Virji, M., Kayhty, H., Ferguson, D.J.P., Alexandrescu, C., Heckels, J.E. and Moxon, E.R. (1991a) The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells. Mol Microbiol 5: 1831–1841.

    Article  PubMed  CAS  Google Scholar 

  28. Virji, M., Kayhty, H., Ferguson, D.J.P., Alexandrescu, C., and Moxon, E.R. (1991b) Interactions of Haemophilus influenzae with cultured human endothelial cells. Microb Pathogen 10: 231–245.

    Article  CAS  Google Scholar 

  29. Virji, M., Alexandrescu, C., Ferguson, D.J.P., Saunders, J.R. and Moxon, E.R. (1992a) Variations in the expression of pili: the effect on adherence of Neisseria meningitidis to human epithelial and endothelial cells. Mol Microbiol 6: 1271–1279.

    Article  PubMed  CAS  Google Scholar 

  30. Virji, M., Makepeace, K., Ferguson, D.J.P., Achtman, M., Sarkari, J. and Moxon, E.R. (1992b) Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis. Mol Microbiol 6: 2785–2795.

    Article  PubMed  CAS  Google Scholar 

  31. Virji, M., Saunders, J.R., Sims, G., Makepeace, K., Maskell, D. and Ferguson, J.R (1993a) Pilus-facilitated adherence of Neisseria meningitidis to human epithelial and endothelial cells: modulation of adherence phenotype occurs concurrently with changes in amino acid sequence and the glycosylation status of pilin. Mol Microbiol 10: 1013–28.

    Article  PubMed  CAS  Google Scholar 

  32. Virji, M., Makepeace, K., Ferguson, D.J.P., Achtman, M. & Moxon, E.R. (1993b). Meningococcal Opa and Opc proteins: their role in colonisation and invasion of human epithelial and endothelial cells. Mol Microbiol 10(3), 499–510.

    Article  PubMed  CAS  Google Scholar 

  33. Virji, M., Makepeace, K. & Moxon, E.R. (1994a). Distinct mechanisms of interaction of Opc-expressing meningococci at apical and basolateral surfaces of human endothelial cells; the role of integrins in apical interactions. Mol Microbiol 14(1), 173–184.

    Article  PubMed  CAS  Google Scholar 

  34. Viiji, M., Makepeace, K. & Moxon, E.R. (1994b). In Neisseria 94. Meningococcal outer-membrane Opc mediates interactions with multiple extracellular matrix components. Proceedings of the Ninth International Pathogenic Neisseria Conference, pp. 263–264. Editors J.S. Evans, S.E. Yost, M.C.J. Maiden and I.M. Feavers.

    Google Scholar 

  35. Virji, M. Makepeace, K., Peak, I., Payne, G., Saunders, J.R., Ferguson, D.J.P. and Moxon, E.R. (1995a) Functional implications of the expression of PilC proteins in meningococci. Mol Microbiol 16(6): 1087–1097.

    Article  PubMed  CAS  Google Scholar 

  36. Virji, M., Makepeace, K., Peak, I.R.A., Ferguson, D.J.P., Jennings, M.P. and Moxon, E.R. (1995b) Opc- and pilus- dependent interactions of meningococci with human endothelial cells: molecular mechanisms and modulation by surface polysaccharides. Mol Microbiol, 18 (4): 741–754.

    Article  PubMed  CAS  Google Scholar 

  37. Virji, M., Stimson, E., Makepeace, K., Dell, A., Morris, H.R., Payne, G., Saunders, J.R. and Moxon, E.R. (1996) Post-translational modifications of meningococcal pili: identification of a common trisaccha- ride substitution on variant pilins of strain C311. In Microbial Pathogenesis and Immune Response II. Annals of The New York Academy of Sciences, (in press).

    Google Scholar 

  38. Wang, J.F., Caugant, D.A., Morelli, G., Koumare, B. and Achtman, M. (1993) Antigenic and epidemiologic properties of the ET-37 complex of Neisseria meningitidis. J Infect 167(6): 1320–1329

    Article  CAS  Google Scholar 

  39. Whittaker, D.V., Parolis, L.A.S. and Parolis, H. (1994) Escherichia coli K48 capsular polysaccharide: a glycan containing a novel diacetamido sugar. Carbohydr Res 256: 289–301.

    Article  Google Scholar 

  40. Zehavi, U. and Sharon, N. (1973) Structural studies of 4-acetamido-2-amino-2,4,6-trideoxy-D-glucose (N- Acetylbacillosamine), the N-acetyl-diamino sugar of Bacillus licheniformis. J. Biol. Chem. 248: 433–438

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Plenum Press, New York

About this chapter

Cite this chapter

Virji, M. (1996). Studies on the Molecular Mechanisms of Meningococcal Interactions with Human Cells. In: Kahane, I., Ofek, I. (eds) Toward Anti-Adhesion Therapy for Microbial Diseases. Advances in Experimental Medicine and Biology, vol 408. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0415-9_13

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0415-9_13

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-8042-9

  • Online ISBN: 978-1-4613-0415-9

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics