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. 1995 Jul;8(3):376–388. doi: 10.1128/cmr.8.3.376

Interaction of pathogenic neisseriae with nonphagocytic cells.

X Nassif 1, M So 1
PMCID: PMC174630  PMID: 7553571

Abstract

The ability to interact with nonphagocytic cells is a crucial virulence attribute of the meningococcus and the genococcus. Like most bacterial pathogens, Neisseria meningitidis and Neisseria gonorrhoeae initiate infections by colonizing the mucosal epithelium, which serves as the site of entry. After this step, both bacteria cross the intact mucosal barrier. While N. gonorrhoeae is likely to remain in the subepithelial matrix, where it initiates an intense inflammatory reaction, N. meningitidis enters the bloodstream, and eventually the cerebrospinal fluid to cause meningitis. Both pathogens have evolved very similar mechanisms for interacting with host cells. Surface structures that influence bacterium-host interactions include pili, the meningococcal class 5 outer membrane proteins or the gonococcal opacity proteins, lipooligosaccharide, and the meningococcal capsule. This review examines what is known about the roles these structures play in bacterial adhesion and invasion, with special emphasis, on pilus-mediated adhesion. Finally, the importance of these structures in neisserial pathogenesis is discussed.

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Selected References

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  1. Achtman M., Neibert M., Crowe B. A., Strittmatter W., Kusecek B., Weyse E., Walsh M. J., Slawig B., Morelli G., Moll A. Purification and characterization of eight class 5 outer membrane protein variants from a clone of Neisseria meningitidis serogroup A. J Exp Med. 1988 Aug 1;168(2):507–525. doi: 10.1084/jem.168.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Aho E. L., Dempsey J. A., Hobbs M. M., Klapper D. G., Cannon J. G. Characterization of the opa (class 5) gene family of Neisseria meningitidis. Mol Microbiol. 1991 Jun;5(6):1429–1437. doi: 10.1111/j.1365-2958.1991.tb00789.x. [DOI] [PubMed] [Google Scholar]
  3. Ala'Aldeen D. A., Powell N. B., Wall R. A., Borriello S. P. Localization of the meningococcal receptors for human transferrin. Infect Immun. 1993 Feb;61(2):751–759. doi: 10.1128/iai.61.2.751-759.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Anderson J. E., Sparling P. F., Cornelissen C. N. Gonococcal transferrin-binding protein 2 facilitates but is not essential for transferrin utilization. J Bacteriol. 1994 Jun;176(11):3162–3170. doi: 10.1128/jb.176.11.3162-3170.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arko R. J. Animal models for pathogenic Neisseria species. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S56–S59. doi: 10.1128/cmr.2.suppl.s56. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Belland R. J., Chen T., Swanson J., Fischer S. H. Human neutrophil response to recombinant neisserial Opa proteins. Mol Microbiol. 1992 Jul;6(13):1729–1737. doi: 10.1111/j.1365-2958.1992.tb01345.x. [DOI] [PubMed] [Google Scholar]
  7. Belland R. J., Morrison S. G., van der Ley P., Swanson J. Expression and phase variation of gonococcal P.II genes in Escherichia coli involves ribosomal frameshifting and slipped-strand mispairing. Mol Microbiol. 1989 Jun;3(6):777–786. doi: 10.1111/j.1365-2958.1989.tb00226.x. [DOI] [PubMed] [Google Scholar]
  8. Bergström S., Robbins K., Koomey J. M., Swanson J. Piliation control mechanisms in Neisseria gonorrhoeae. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3890–3894. doi: 10.1073/pnas.83.11.3890. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Bessen D., Gotschlich E. C. Interactions of gonococci with HeLa cells: attachment, detachment, replication, penetration, and the role of protein II. Infect Immun. 1986 Oct;54(1):154–160. doi: 10.1128/iai.54.1.154-160.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bhat K. S., Gibbs C. P., Barrera O., Morrison S. G., Jähnig F., Stern A., Kupsch E. M., Meyer T. F., Swanson J. The opacity proteins of Neisseria gonorrhoeae strain MS11 are encoded by a family of 11 complete genes. Mol Microbiol. 1991 Aug;5(8):1889–1901. doi: 10.1111/j.1365-2958.1991.tb00813.x. [DOI] [PubMed] [Google Scholar]
  11. Bohnhoff M., Morello J. A., Lerner S. A. Auxotypes, penicillin susceptibility, and serogroups of Neisseria gonorrhoeae from disseminated and uncomplicated infections. J Infect Dis. 1986 Aug;154(2):225–230. doi: 10.1093/infdis/154.2.225. [DOI] [PubMed] [Google Scholar]
  12. Boxberger H. J., Sessler M. J., Maetzel B., Meyer T. F. Highly polarized primary epithelial cells from human nasopharynx grown as spheroid-like vesicles. Eur J Cell Biol. 1993 Oct;62(1):140–151. [PubMed] [Google Scholar]
  13. Chen J. C., Bavoil P., Clark V. L. Enhancement of the invasive ability of Neisseria gonorrhoeae by contact with HecIB, an adenocarcinoma endometrial cell line. Mol Microbiol. 1991 Jun;5(6):1531–1538. doi: 10.1111/j.1365-2958.1991.tb00800.x. [DOI] [PubMed] [Google Scholar]
  14. Cohen M. S., Cannon J. G., Jerse A. E., Charniga L. M., Isbey S. F., Whicker L. G. Human experimentation with Neisseria gonorrhoeae: rationale, methods, and implications for the biology of infection and vaccine development. J Infect Dis. 1994 Mar;169(3):532–537. doi: 10.1093/infdis/169.3.532. [DOI] [PubMed] [Google Scholar]
  15. Connell T. D., Shaffer D., Cannon J. G. Characterization of the repertoire of hypervariable regions in the Protein II (opa) gene family of Neisseria gonorrhoeae. Mol Microbiol. 1990 Mar;4(3):439–449. doi: 10.1111/j.1365-2958.1990.tb00610.x. [DOI] [PubMed] [Google Scholar]
  16. Cooper M. D., McGee Z. A., Mulks M. H., Koomey J. M., Hindman T. L. Attachment to and invasion of human fallopian tube mucosa by an IgA1 protease-deficient mutant of Neisseria gonorrhoeae and its wild-type parent. J Infect Dis. 1984 Nov;150(5):737–744. doi: 10.1093/infdis/150.5.737. [DOI] [PubMed] [Google Scholar]
  17. Cornelissen C. N., Biswas G. D., Tsai J., Paruchuri D. K., Thompson S. A., Sparling P. F. Gonococcal transferrin-binding protein 1 is required for transferrin utilization and is homologous to TonB-dependent outer membrane receptors. J Bacteriol. 1992 Sep;174(18):5788–5797. doi: 10.1128/jb.174.18.5788-5797.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Cornelissen C. N., Sparling P. F. Iron piracy: acquisition of transferrin-bound iron by bacterial pathogens. Mol Microbiol. 1994 Dec;14(5):843–850. doi: 10.1111/j.1365-2958.1994.tb01320.x. [DOI] [PubMed] [Google Scholar]
  19. Dalrymple B., Mattick J. S. An analysis of the organization and evolution of type 4 fimbrial (MePhe) subunit proteins. J Mol Evol. 1987;25(3):261–269. doi: 10.1007/BF02100020. [DOI] [PubMed] [Google Scholar]
  20. DeVoe I. W., Gilchrist J. E. Pili on meningococci from primary cultures of nasopharyngeal carriers and cerebrospinal fluid of patients with acute disease. J Exp Med. 1975 Feb 1;141(2):297–305. doi: 10.1084/jem.141.2.297. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. DeVoe I. W. The meningococcus and mechanisms of pathogenicity. Microbiol Rev. 1982 Jun;46(2):162–190. doi: 10.1128/mr.46.2.162-190.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Dehouck M. P., Jolliet-Riant P., Brée F., Fruchart J. C., Cecchelli R., Tillement J. P. Drug transfer across the blood-brain barrier: correlation between in vitro and in vivo models. J Neurochem. 1992 May;58(5):1790–1797. doi: 10.1111/j.1471-4159.1992.tb10055.x. [DOI] [PubMed] [Google Scholar]
  23. Dempsey J. A., Cannon J. G. Locations of genetic markers on the physical map of the chromosome of Neisseria gonorrhoeae FA1090. J Bacteriol. 1994 Apr;176(7):2055–2060. doi: 10.1128/jb.176.7.2055-2060.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Dempsey J. A., Litaker W., Madhure A., Snodgrass T. L., Cannon J. G. Physical map of the chromosome of Neisseria gonorrhoeae FA1090 with locations of genetic markers, including opa and pil genes. J Bacteriol. 1991 Sep;173(17):5476–5486. doi: 10.1128/jb.173.17.5476-5486.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Duckworth M., Jackson D., Zak K., Heckels J. E. Structural variations in pili expressed during gonococcal infection. J Gen Microbiol. 1983 May;129(5):1593–1596. doi: 10.1099/00221287-129-5-1593. [DOI] [PubMed] [Google Scholar]
  26. Frangipane J. V., Rest R. F. Anaerobic growth and cytidine 5'-monophospho-N-acetylneuraminic acid act synergistically to induce high-level serum resistance in Neisseria gonorrhoeae. Infect Immun. 1993 May;61(5):1657–1666. doi: 10.1128/iai.61.5.1657-1666.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Gibbs C. P., Reimann B. Y., Schultz E., Kaufmann A., Haas R., Meyer T. F. Reassortment of pilin genes in Neisseria gonorrhoeae occurs by two distinct mechanisms. Nature. 1989 Apr 20;338(6217):651–652. doi: 10.1038/338651a0. [DOI] [PubMed] [Google Scholar]
  28. Gorby G., Simon D., Rest R. F. Escherichia coli that express Neisseria gonorrhoeae opacity-associated proteins attach to and invade human fallopian tube epithelium. Ann N Y Acad Sci. 1994 Aug 15;730:286–289. doi: 10.1111/j.1749-6632.1994.tb44267.x. [DOI] [PubMed] [Google Scholar]
  29. Greenblatt J. J., Floyd K., Philipps M. E., Frasch C. E. Morphological differences in Neisseria meningitidis pili. Infect Immun. 1988 Sep;56(9):2356–2362. doi: 10.1128/iai.56.9.2356-2362.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Greenfield S., Feldman H. A. Familial carriers and meningococcal meningitis. N Engl J Med. 1967 Sep 7;277(10):487–502. doi: 10.1056/NEJM196709072771001. [DOI] [PubMed] [Google Scholar]
  31. Greenfield S., Sheehe P. R., Feldman H. A. Meningococcal carriage in a population of "normal" families. J Infect Dis. 1971 Jan;123(1):67–73. doi: 10.1093/infdis/123.1.67. [DOI] [PubMed] [Google Scholar]
  32. Gregg C. R., Johnson A. P., Taylor-Robinson D., Melly M. A., McGee Z. A. Host species-specific damage to oviduct mucosa by Neisseria gonorrhoeae lipopolysaccharide. Infect Immun. 1981 Dec;34(3):1056–1058. doi: 10.1128/iai.34.3.1056-1058.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Gregg C. R., Melly M. A., Hellerqvist C. G., Coniglio J. G., McGee Z. A. Toxic activity of purified lipopolysaccharide of Neisseria gonorrhoeae for human fallopian tube mucosa. J Infect Dis. 1981 Mar;143(3):432–439. doi: 10.1093/infdis/143.3.432. [DOI] [PubMed] [Google Scholar]
  34. Guibourdenche M., Popoff M. Y., Riou J. Y. Deoxyribonucleic acid relatedness among Neisseria gonorrhoeae, N. meningitidis, N. lactamica, N. cinerea and "Neisseria polysaccharea". Ann Inst Pasteur Microbiol. 1986 Sep-Oct;137B(2):177–185. doi: 10.1016/s0769-2609(86)80106-5. [DOI] [PubMed] [Google Scholar]
  35. Hagblom P., Segal E., Billyard E., So M. Intragenic recombination leads to pilus antigenic variation in Neisseria gonorrhoeae. Nature. 1985 May 9;315(6015):156–158. doi: 10.1038/315156a0. [DOI] [PubMed] [Google Scholar]
  36. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  37. Higgins D. G., Sharp P. M. Fast and sensitive multiple sequence alignments on a microcomputer. Comput Appl Biosci. 1989 Apr;5(2):151–153. doi: 10.1093/bioinformatics/5.2.151. [DOI] [PubMed] [Google Scholar]
  38. Hoehn G. T., Clark V. L. The major anaerobically induced outer membrane protein of Neisseria gonorrhoeae, Pan 1, is a lipoprotein. Infect Immun. 1992 Nov;60(11):4704–4708. doi: 10.1128/iai.60.11.4704-4708.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Holbein B. E. Iron-controlled infection with Neisseria meningitidis in mice. Infect Immun. 1980 Sep;29(3):886–891. doi: 10.1128/iai.29.3.886-891.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Irwin S. W., Averil N., Cheng C. Y., Schryvers A. B. Preparation and analysis of isogenic mutants in the transferrin receptor protein genes, tbpA and tbpB, from Neisseria meningitidis. Mol Microbiol. 1993 Jun;8(6):1125–1133. doi: 10.1111/j.1365-2958.1993.tb01657.x. [DOI] [PubMed] [Google Scholar]
  41. Jarvis G. A., Vedros N. A. Sialic acid of group B Neisseria meningitidis regulates alternative complement pathway activation. Infect Immun. 1987 Jan;55(1):174–180. doi: 10.1128/iai.55.1.174-180.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Jerse A. E., Cohen M. S., Drown P. M., Whicker L. G., Isbey S. F., Seifert H. S., Cannon J. G. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J Exp Med. 1994 Mar 1;179(3):911–920. doi: 10.1084/jem.179.3.911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. Johnson S. C., Chung R. C., Deal C. D., Boslego J. W., Sadoff J. C., Wood S. W., Brinton C. C., Jr, Tramont E. C. Human immunization with Pgh 3-2 gonococcal pilus results in cross-reactive antibody to the cyanogen bromide fragment-2 of pilin. J Infect Dis. 1991 Jan;163(1):128–134. doi: 10.1093/infdis/163.1.128. [DOI] [PubMed] [Google Scholar]
  44. Jones B. D., Ghori N., Falkow S. Salmonella typhimurium initiates murine infection by penetrating and destroying the specialized epithelial M cells of the Peyer's patches. J Exp Med. 1994 Jul 1;180(1):15–23. doi: 10.1084/jem.180.1.15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Jonsson A. B., Ilver D., Falk P., Pepose J., Normark S. Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue. Mol Microbiol. 1994 Aug;13(3):403–416. doi: 10.1111/j.1365-2958.1994.tb00435.x. [DOI] [PubMed] [Google Scholar]
  46. Jonsson A. B., Nyberg G., Normark S. Phase variation of gonococcal pili by frameshift mutation in pilC, a novel gene for pilus assembly. EMBO J. 1991 Feb;10(2):477–488. doi: 10.1002/j.1460-2075.1991.tb07970.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Jonsson A. B., Pfeifer J., Normark S. Neisseria gonorrhoeae PilC expression provides a selective mechanism for structural diversity of pili. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3204–3208. doi: 10.1073/pnas.89.8.3204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Knapp J. S., Holmes K. K. Disseminated gonococcal infections caused by Neisseria gonorrhoeae with unique nutritional requirements. J Infect Dis. 1975 Aug;132(2):204–208. doi: 10.1093/infdis/132.2.204. [DOI] [PubMed] [Google Scholar]
  49. Kupsch E. M., Knepper B., Kuroki T., Heuer I., Meyer T. F. Variable opacity (Opa) outer membrane proteins account for the cell tropisms displayed by Neisseria gonorrhoeae for human leukocytes and epithelial cells. EMBO J. 1993 Feb;12(2):641–650. doi: 10.1002/j.1460-2075.1993.tb05697.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Lambden P. R., Heckels J. E., Watt P. J. Effect of anti-pilus antibodies on survival of gonococci within guinea pig subcutaneous chambers. Infect Immun. 1982 Oct;38(1):27–30. doi: 10.1128/iai.38.1.27-30.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Lambden P. R., Robertson J. N., Watt P. J. Biological properties of two distinct pilus types produced by isogenic variants of Neisseria gonorrhoeae P9. J Bacteriol. 1980 Jan;141(1):393–396. doi: 10.1128/jb.141.1.393-396.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Mahan M. J., Slauch J. M., Mekalanos J. J. Selection of bacterial virulence genes that are specifically induced in host tissues. Science. 1993 Jan 29;259(5095):686–688. doi: 10.1126/science.8430319. [DOI] [PubMed] [Google Scholar]
  53. Makino S., van Putten J. P., Meyer T. F. Phase variation of the opacity outer membrane protein controls invasion by Neisseria gonorrhoeae into human epithelial cells. EMBO J. 1991 Jun;10(6):1307–1315. doi: 10.1002/j.1460-2075.1991.tb07649.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Mandrell R. E., Griffiss J. M., Macher B. A. Lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis have components that are immunochemically similar to precursors of human blood group antigens. Carbohydrate sequence specificity of the mouse monoclonal antibodies that recognize crossreacting antigens on LOS and human erythrocytes. J Exp Med. 1988 Jul 1;168(1):107–126. doi: 10.1084/jem.168.1.107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Mandrell R. E., Lesse A. J., Sugai J. V., Shero M., Griffiss J. M., Cole J. A., Parsons N. J., Smith H., Morse S. A., Apicella M. A. In vitro and in vivo modification of Neisseria gonorrhoeae lipooligosaccharide epitope structure by sialylation. J Exp Med. 1990 May 1;171(5):1649–1664. doi: 10.1084/jem.171.5.1649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Martel N., Lee B. C. Acquisition of heme iron by Neisseria meningitidis does not involve meningococcal transferrin-binding proteins. Infect Immun. 1994 Feb;62(2):700–703. doi: 10.1128/iai.62.2.700-703.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Mattick J. S., Anderson B. J., Cox P. T., Dalrymple B. P., Bills M. M., Hobbs M., Egerton J. R. Gene sequences and comparison of the fimbrial subunits representative of Bacteroides nodosus serotypes A to I: class I and class II strains. Mol Microbiol. 1991 Mar;5(3):561–573. doi: 10.1111/j.1365-2958.1991.tb00727.x. [DOI] [PubMed] [Google Scholar]
  58. McGee Z. A., Johnson A. P., Taylor-Robinson D. Pathogenic mechanisms of Neisseria gonorrhoeae: observations on damage to human fallopian tubes in organ culture by gonococci of colony type 1 or type 4. J Infect Dis. 1981 Mar;143(3):413–422. doi: 10.1093/infdis/143.3.413. [DOI] [PubMed] [Google Scholar]
  59. McGee Z. A., Stephens D. S. Common pathways of invasion of mucosal barriers by Neisseria gonorrhoeae and Neisseria meningitidis. Surv Synth Pathol Res. 1984;3(1):1–10. [PubMed] [Google Scholar]
  60. McGee Z. A., Stephens D. S., Hoffman L. H., Schlech W. F., 3rd, Horn R. G. Mechanisms of mucosal invasion by pathogenic Neisseria. Rev Infect Dis. 1983 Sep-Oct;5 (Suppl 4):S708–S714. doi: 10.1093/clinids/5.supplement_4.s708. [DOI] [PubMed] [Google Scholar]
  61. McKenna W. R., Mickelsen P. A., Sparling P. F., Dyer D. W. Iron uptake from lactoferrin and transferrin by Neisseria gonorrhoeae. Infect Immun. 1988 Apr;56(4):785–791. doi: 10.1128/iai.56.4.785-791.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Mekalanos J. J. Environmental signals controlling expression of virulence determinants in bacteria. J Bacteriol. 1992 Jan;174(1):1–7. doi: 10.1128/jb.174.1.1-7.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  63. Melly M. A., Gregg C. R., McGee Z. A. Studies of toxicity of Neisseria gonorrhoeae for human fallopian tube mucosa. J Infect Dis. 1981 Mar;143(3):423–431. doi: 10.1093/infdis/143.3.423. [DOI] [PubMed] [Google Scholar]
  64. Melly M. A., McGee Z. A., Rosenthal R. S. Ability of monomeric peptidoglycan fragments from Neisseria gonorrhoeae to damage human fallopian-tube mucosa. J Infect Dis. 1984 Mar;149(3):378–386. doi: 10.1093/infdis/149.3.378. [DOI] [PubMed] [Google Scholar]
  65. Meyer T. F., Gibbs C. P., Haas R. Variation and control of protein expression in Neisseria. Annu Rev Microbiol. 1990;44:451–477. doi: 10.1146/annurev.mi.44.100190.002315. [DOI] [PubMed] [Google Scholar]
  66. Miller C. P. EXPERIMENTAL MENINGOCOCCAL INFECTION IN MICE. Science. 1933 Oct 13;78(2024):340–341. doi: 10.1126/science.78.2024.340. [DOI] [PubMed] [Google Scholar]
  67. Miller J. F., Mekalanos J. J., Falkow S. Coordinate regulation and sensory transduction in the control of bacterial virulence. Science. 1989 Feb 17;243(4893):916–922. doi: 10.1126/science.2537530. [DOI] [PubMed] [Google Scholar]
  68. Moxon E. R., Rainey P. B., Nowak M. A., Lenski R. E. Adaptive evolution of highly mutable loci in pathogenic bacteria. Curr Biol. 1994 Jan 1;4(1):24–33. doi: 10.1016/s0960-9822(00)00005-1. [DOI] [PubMed] [Google Scholar]
  69. Murphy G. L., Connell T. D., Barritt D. S., Koomey M., Cannon J. G. Phase variation of gonococcal protein II: regulation of gene expression by slipped-strand mispairing of a repetitive DNA sequence. Cell. 1989 Feb 24;56(4):539–547. doi: 10.1016/0092-8674(89)90577-1. [DOI] [PubMed] [Google Scholar]
  70. Nash S., Stafford J., Madara J. L. Effects of polymorphonuclear leukocyte transmigration on the barrier function of cultured intestinal epithelial monolayers. J Clin Invest. 1987 Oct;80(4):1104–1113. doi: 10.1172/JCI113167. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Nassif X., Beretti J. L., Lowy J., Stenberg P., O'Gaora P., Pfeifer J., Normark S., So M. Roles of pilin and PilC in adhesion of Neisseria meningitidis to human epithelial and endothelial cells. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3769–3773. doi: 10.1073/pnas.91.9.3769. [DOI] [PMC free article] [PubMed] [Google Scholar]
  72. Nassif X., Lowy J., Stenberg P., O'Gaora P., Ganji A., So M. Antigenic variation of pilin regulates adhesion of Neisseria meningitidis to human epithelial cells. Mol Microbiol. 1993 May;8(4):719–725. doi: 10.1111/j.1365-2958.1993.tb01615.x. [DOI] [PubMed] [Google Scholar]
  73. Nassif X., Mathison J. C., Wolfson E., Koziol J. A., Ulevitch R. J., So M. Tumour necrosis factor alpha antibody protects against lethal meningococcaemia. Mol Microbiol. 1992 Mar;6(5):591–597. doi: 10.1111/j.1365-2958.1992.tb01505.x. [DOI] [PubMed] [Google Scholar]
  74. Neutra M. R., Kraehenbuhl J. P. Transepithelial transport and mucosal defence I: the role of M cells. Trends Cell Biol. 1992 May;2(5):134–138. doi: 10.1016/0962-8924(92)90099-9. [DOI] [PubMed] [Google Scholar]
  75. Nicolson I. J., Perry A. C., Virji M., Heckels J. E., Saunders J. R. Localization of antibody-binding sites by sequence analysis of cloned pilin genes from Neisseria gonorrhoeae. J Gen Microbiol. 1987 Apr;133(4):825–833. doi: 10.1099/00221287-133-4-825. [DOI] [PubMed] [Google Scholar]
  76. Olafson R. W., McCarthy P. J., Bhatti A. R., Dooley J. S., Heckels J. E., Trust T. J. Structural and antigenic analysis of meningococcal piliation. Infect Immun. 1985 May;48(2):336–342. doi: 10.1128/iai.48.2.336-342.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  77. Olyhoek A. J., Sarkari J., Bopp M., Morelli G., Achtman M. Cloning and expression in Escherichia coli of opc, the gene for an unusual class 5 outer membrane protein from Neisseria meningitidis (meningococci/surface antigen). Microb Pathog. 1991 Oct;11(4):249–257. doi: 10.1016/0882-4010(91)90029-a. [DOI] [PubMed] [Google Scholar]
  78. Parkinson J. S. Signal transduction schemes of bacteria. Cell. 1993 Jun 4;73(5):857–871. doi: 10.1016/0092-8674(93)90267-t. [DOI] [PubMed] [Google Scholar]
  79. Paruchuri D. K., Seifert H. S., Ajioka R. S., Karlsson K. A., So M. Identification and characterization of a Neisseria gonorrhoeae gene encoding a glycolipid-binding adhesin. Proc Natl Acad Sci U S A. 1990 Jan;87(1):333–337. doi: 10.1073/pnas.87.1.333. [DOI] [PMC free article] [PubMed] [Google Scholar]
  80. Perry A. C., Nicolson I. J., Saunders J. R. Neisseria meningitidis C114 contains silent, truncated pilin genes that are homologous to Neisseria gonorrhoeae pil sequences. J Bacteriol. 1988 Apr;170(4):1691–1697. doi: 10.1128/jb.170.4.1691-1697.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Pettersson A., Maas A., Tommassen J. Identification of the iroA gene product of Neisseria meningitidis as a lactoferrin receptor. J Bacteriol. 1994 Mar;176(6):1764–1766. doi: 10.1128/jb.176.6.1764-1766.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. Potts W. J., Saunders J. R. Nucleotide sequence of the structural gene for class I pilin from Neisseria meningitidis: homologies with the pilE locus of Neisseria gonorrhoeae. Mol Microbiol. 1988 Sep;2(5):647–653. doi: 10.1111/j.1365-2958.1988.tb00073.x. [DOI] [PubMed] [Google Scholar]
  83. Punsalang A. P., Jr, Sawyer W. D. Role of pili in the virulence of Neisseria gonorrhoeae. Infect Immun. 1973 Aug;8(2):255–263. doi: 10.1128/iai.8.2.255-263.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  84. Rothbard J. B., Fernandez R., Wang L., Teng N. N., Schoolnik G. K. Antibodies to peptides corresponding to a conserved sequence of gonococcal pilins block bacterial adhesion. Proc Natl Acad Sci U S A. 1985 Feb;82(3):915–919. doi: 10.1073/pnas.82.3.915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  85. Rudel T., Scheurerpflug I., Meyer T. F. Neisseria PilC protein identified as type-4 pilus tip-located adhesin. Nature. 1995 Jan 26;373(6512):357–359. doi: 10.1038/373357a0. [DOI] [PubMed] [Google Scholar]
  86. Rudel T., van Putten J. P., Gibbs C. P., Haas R., Meyer T. F. Interaction of two variable proteins (PilE and PilC) required for pilus-mediated adherence of Neisseria gonorrhoeae to human epithelial cells. Mol Microbiol. 1992 Nov;6(22):3439–3450. doi: 10.1111/j.1365-2958.1992.tb02211.x. [DOI] [PubMed] [Google Scholar]
  87. Salit I. E. Hemagglutination by Neisseria meningitidis. Can J Microbiol. 1981 Jun;27(6):586–593. doi: 10.1139/m81-089. [DOI] [PubMed] [Google Scholar]
  88. Sarkari J., Pandit N., Moxon E. R., Achtman M. Variable expression of the Opc outer membrane protein in Neisseria meningitidis is caused by size variation of a promoter containing poly-cytidine. Mol Microbiol. 1994 Jul;13(2):207–217. doi: 10.1111/j.1365-2958.1994.tb00416.x. [DOI] [PubMed] [Google Scholar]
  89. Saukkonen K., Abdillahi H., Poolman J. T., Leinonen M. Protective efficacy of monoclonal antibodies to class 1 and class 3 outer membrane proteins of Neisseria meningitidis B:15:P1.16 in infant rat infection model: new prospects for vaccine development. Microb Pathog. 1987 Oct;3(4):261–267. doi: 10.1016/0882-4010(87)90059-3. [DOI] [PubMed] [Google Scholar]
  90. Schneider H., Griffiss J. M., Boslego J. W., Hitchcock P. J., Zahos K. M., Apicella M. A. Expression of paragloboside-like lipooligosaccharides may be a necessary component of gonococcal pathogenesis in men. J Exp Med. 1991 Dec 1;174(6):1601–1605. doi: 10.1084/jem.174.6.1601. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Schneider H., Hale T. L., Zollinger W. D., Seid R. C., Jr, Hammack C. A., Griffiss J. M. Heterogeneity of molecular size and antigenic expression within lipooligosaccharides of individual strains of Neisseria gonorrhoeae and Neisseria meningitidis. Infect Immun. 1984 Sep;45(3):544–549. doi: 10.1128/iai.45.3.544-549.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Schryvers A. B., Morris L. J. Identification and characterization of the human lactoferrin-binding protein from Neisseria meningitidis. Infect Immun. 1988 May;56(5):1144–1149. doi: 10.1128/iai.56.5.1144-1149.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Schryvers A. B., Morris L. J. Identification and characterization of the transferrin receptor from Neisseria meningitidis. Mol Microbiol. 1988 Mar;2(2):281–288. doi: 10.1111/j.1365-2958.1988.tb00029.x. [DOI] [PubMed] [Google Scholar]
  94. Seifert H. S., Ajioka R. S., Marchal C., Sparling P. F., So M. DNA transformation leads to pilin antigenic variation in Neisseria gonorrhoeae. Nature. 1988 Nov 24;336(6197):392–395. doi: 10.1038/336392a0. [DOI] [PubMed] [Google Scholar]
  95. Seifert H. S., So M. Genetic mechanisms of bacterial antigenic variation. Microbiol Rev. 1988 Sep;52(3):327–336. doi: 10.1128/mr.52.3.327-336.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Seifert H. S., Wright C. J., Jerse A. E., Cohen M. S., Cannon J. G. Multiple gonococcal pilin antigenic variants are produced during experimental human infections. J Clin Invest. 1994 Jun;93(6):2744–2749. doi: 10.1172/JCI117290. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Shaw J. H., Falkow S. Model for invasion of human tissue culture cells by Neisseria gonorrhoeae. Infect Immun. 1988 Jun;56(6):1625–1632. doi: 10.1128/iai.56.6.1625-1632.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  98. Simon D., Rest R. F. Escherichia coli expressing a Neisseria gonorrhoeae opacity-associated outer membrane protein invade human cervical and endometrial epithelial cell lines. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5512–5516. doi: 10.1073/pnas.89.12.5512. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Sparling P. F., Cannon J. G., So M. Phase and antigenic variation of pili and outer membrane protein II of Neisseria gonorrhoeae. J Infect Dis. 1986 Feb;153(2):196–201. doi: 10.1093/infdis/153.2.196. [DOI] [PubMed] [Google Scholar]
  100. Stephens D. S. Gonococcal and meningococcal pathogenesis as defined by human cell, cell culture, and organ culture assays. Clin Microbiol Rev. 1989 Apr;2 (Suppl):S104–S111. doi: 10.1128/cmr.2.suppl.s104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  101. Stephens D. S., Hoffman L. H., McGee Z. A. Interaction of Neisseria meningitidis with human nasopharyngeal mucosa: attachment and entry into columnar epithelial cells. J Infect Dis. 1983 Sep;148(3):369–376. doi: 10.1093/infdis/148.3.369. [DOI] [PubMed] [Google Scholar]
  102. Stephens D. S., Krebs J. W., McGee Z. A. Loss of pili and decreased attachment to human cells by Neisseria meningitidis and Neisseria gonorrhoeae exposed to subinhibitory concentrations of antibiotics. Infect Immun. 1984 Nov;46(2):507–513. doi: 10.1128/iai.46.2.507-513.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  103. Stephens D. S., McGee Z. A. Attachment of Neisseria meningitidis to human mucosal surfaces: influence of pili and type of receptor cell. J Infect Dis. 1981 Apr;143(4):525–532. doi: 10.1093/infdis/143.4.525. [DOI] [PubMed] [Google Scholar]
  104. Stephens D. S., Spellman P. A., Swartley J. S. Effect of the (alpha 2-->8)-linked polysialic acid capsule on adherence of Neisseria meningitidis to human mucosal cells. J Infect Dis. 1993 Feb;167(2):475–479. doi: 10.1093/infdis/167.2.475. [DOI] [PubMed] [Google Scholar]
  105. Stephens D. S., Whitney A. M., Melly M. A., Hoffman L. H., Farley M. M., Frasch C. E. Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis. Infect Immun. 1986 Feb;51(2):579–585. doi: 10.1128/iai.51.2.579-585.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Stern A., Brown M., Nickel P., Meyer T. F. Opacity genes in Neisseria gonorrhoeae: control of phase and antigenic variation. Cell. 1986 Oct 10;47(1):61–71. doi: 10.1016/0092-8674(86)90366-1. [DOI] [PubMed] [Google Scholar]
  107. Stern A., Meyer T. F. Common mechanism controlling phase and antigenic variation in pathogenic neisseriae. Mol Microbiol. 1987 Jul;1(1):5–12. doi: 10.1111/j.1365-2958.1987.tb00520.x. [DOI] [PubMed] [Google Scholar]
  108. Stern A., Nickel P., Meyer T. F., So M. Opacity determinants of Neisseria gonorrhoeae: gene expression and chromosomal linkage to the gonococcal pilus gene. Cell. 1984 Jun;37(2):447–456. doi: 10.1016/0092-8674(84)90375-1. [DOI] [PubMed] [Google Scholar]
  109. Stojiljkovic I., Hwa V., de Saint Martin L., O'Gaora P., Nassif X., Heffron F., So M. The Neisseria meningitidis haemoglobin receptor: its role in iron utilization and virulence. Mol Microbiol. 1995 Feb;15(3):531–541. doi: 10.1111/j.1365-2958.1995.tb02266.x. [DOI] [PubMed] [Google Scholar]
  110. Sugasawara R. J., Cannon J. G., Black W. J., Nachamkin I., Sweet R. L., Brooks G. F. Inhibition of Neisseria gonorrhoeae attachment to HeLa cells with monoclonal antibody directed against a protein II. Infect Immun. 1983 Dec;42(3):980–985. doi: 10.1128/iai.42.3.980-985.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  111. Swanson J. 125I-labeled peptide mapping of some heat-modifiable proteins of the gonococcal outer membrane. Infect Immun. 1980 Apr;28(1):54–64. doi: 10.1128/iai.28.1.54-64.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Swanson J., Bergström S., Robbins K., Barrera O., Corwin D., Koomey J. M. Gene conversion involving the pilin structural gene correlates with pilus+ in equilibrium with pilus- changes in Neisseria gonorrhoeae. Cell. 1986 Oct 24;47(2):267–276. doi: 10.1016/0092-8674(86)90449-6. [DOI] [PubMed] [Google Scholar]
  113. Swanson J., Robbins K., Barrera O., Koomey J. M. Gene conversion variations generate structurally distinct pilin polypeptides in Neisseria gonorrhoeae. J Exp Med. 1987 Apr 1;165(4):1016–1025. doi: 10.1084/jem.165.4.1016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. Swanson J. Studies on gonococcus infection. IV. Pili: their role in attachment of gonococci to tissue culture cells. J Exp Med. 1973 Mar 1;137(3):571–589. doi: 10.1084/jem.137.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  115. Taha M. K., Dupuy B., Saurin W., So M., Marchal C. Control of pilus expression in Neisseria gonorrhoeae as an original system in the family of two-component regulators. Mol Microbiol. 1991 Jan;5(1):137–148. doi: 10.1111/j.1365-2958.1991.tb01834.x. [DOI] [PubMed] [Google Scholar]
  116. Taha M. K., Marchal C. Conservation of Neisseria gonorrhoeae pilus expression regulatory genes pilA and pilB in the genus Neisseria. Infect Immun. 1990 Dec;58(12):4145–4148. doi: 10.1128/iai.58.12.4145-4148.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  117. Taha M. K., So M., Seifert H. S., Billyard E., Marchal C. Pilin expression in Neisseria gonorrhoeae is under both positive and negative transcriptional control. EMBO J. 1988 Dec 20;7(13):4367–4378. doi: 10.1002/j.1460-2075.1988.tb03335.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  118. Thompson S. A., Sparling P. F. The RTX cytotoxin-related FrpA protein of Neisseria meningitidis is secreted extracellularly by meningococci and by HlyBD+ Escherichia coli. Infect Immun. 1993 Jul;61(7):2906–2911. doi: 10.1128/iai.61.7.2906-2911.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  119. Thompson S. A., Wang L. L., Sparling P. F. Cloning and nucleotide sequence of frpC, a second gene from Neisseria meningitidis encoding a protein similar to RTX cytotoxins. Mol Microbiol. 1993 Jul;9(1):85–96. doi: 10.1111/j.1365-2958.1993.tb01671.x. [DOI] [PubMed] [Google Scholar]
  120. Thompson S. A., Wang L. L., West A., Sparling P. F. Neisseria meningitidis produces iron-regulated proteins related to the RTX family of exoproteins. J Bacteriol. 1993 Feb;175(3):811–818. doi: 10.1128/jb.175.3.811-818.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  121. Tinsley C. R., Heckels J. E. Variation in the expression of pili and outer membrane protein by Neisseria meningitidis during the course of meningococcal infection. J Gen Microbiol. 1986 Sep;132(9):2483–2490. doi: 10.1099/00221287-132-9-2483. [DOI] [PubMed] [Google Scholar]
  122. Tsai C. M., Frasch C. E., Mocca L. F. Five structural classes of major outer membrane proteins in Neisseria meningitidis. J Bacteriol. 1981 Apr;146(1):69–78. doi: 10.1128/jb.146.1.69-78.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Virji M., Alexandrescu C., Ferguson D. J., Saunders J. R., Moxon E. R. Variations in the expression of pili: the effect on adherence of Neisseria meningitidis to human epithelial and endothelial cells. Mol Microbiol. 1992 May;6(10):1271–1279. doi: 10.1111/j.1365-2958.1992.tb00848.x. [DOI] [PubMed] [Google Scholar]
  124. Virji M., Heckels J. E. Antigenic cross-reactivity of Neisseria pili: investigations with type- and species-specific monoclonal antibodies. J Gen Microbiol. 1983 Sep;129(9):2761–2768. doi: 10.1099/00221287-129-9-2761. [DOI] [PubMed] [Google Scholar]
  125. Virji M., Heckels J. E., Potts W. J., Hart C. A., Saunders J. R. Identification of epitopes recognized by monoclonal antibodies SM1 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. 1989 Dec;135(12):3239–3251. doi: 10.1099/00221287-135-12-3239. [DOI] [PubMed] [Google Scholar]
  126. Virji M., Kayhty H., Ferguson D. J., Alexandrescu C., Heckels J. E., Moxon E. R. The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells. Mol Microbiol. 1991 Aug;5(8):1831–1841. doi: 10.1111/j.1365-2958.1991.tb00807.x. [DOI] [PubMed] [Google Scholar]
  127. Virji M., Makepeace K., Ferguson D. J., Achtman M., Moxon E. R. Meningococcal Opa and Opc proteins: their role in colonization and invasion of human epithelial and endothelial cells. Mol Microbiol. 1993 Nov;10(3):499–510. doi: 10.1111/j.1365-2958.1993.tb00922.x. [DOI] [PubMed] [Google Scholar]
  128. Virji M., Makepeace K., Ferguson D. J., Achtman M., Sarkari J., Moxon E. R. Expression of the Opc protein correlates with invasion of epithelial and endothelial cells by Neisseria meningitidis. Mol Microbiol. 1992 Oct;6(19):2785–2795. doi: 10.1111/j.1365-2958.1992.tb01458.x. [DOI] [PubMed] [Google Scholar]
  129. Virji M., Saunders J. R., Sims G., Makepeace K., Maskell D., Ferguson D. J. 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. 1993 Dec;10(5):1013–1028. doi: 10.1111/j.1365-2958.1993.tb00972.x. [DOI] [PubMed] [Google Scholar]
  130. Waldbeser L. S., Ajioka R. S., Merz A. J., Puaoi D., Lin L., Thomas M., So M. The opaH locus of Neisseria gonorrhoeae MS11A is involved in epithelial cell invasion. Mol Microbiol. 1994 Sep;13(5):919–928. doi: 10.1111/j.1365-2958.1994.tb00483.x. [DOI] [PubMed] [Google Scholar]
  131. Weel J. F., Hopman C. T., van Putten J. P. Bacterial entry and intracellular processing of Neisseria gonorrhoeae in epithelial cells: immunomorphological evidence for alterations in the major outer membrane protein P.IB. J Exp Med. 1991 Sep 1;174(3):705–715. doi: 10.1084/jem.174.3.705. [DOI] [PMC free article] [PubMed] [Google Scholar]
  132. Weel J. F., Hopman C. T., van Putten J. P. In situ expression and localization of Neisseria gonorrhoeae opacity proteins in infected epithelial cells: apparent role of Opa proteins in cellular invasion. J Exp Med. 1991 Jun 1;173(6):1395–1405. doi: 10.1084/jem.173.6.1395. [DOI] [PMC free article] [PubMed] [Google Scholar]
  133. Woods J. P., Cannon J. G. Variation in expression of class 1 and class 5 outer membrane proteins during nasopharyngeal carriage of Neisseria meningitidis. Infect Immun. 1990 Feb;58(2):569–572. doi: 10.1128/iai.58.2.569-572.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  134. Zak K., Diaz J. L., Jackson D., Heckels J. E. Antigenic variation during infection with Neisseria gonorrhoeae: detection of antibodies to surface proteins in sera of patients with gonorrhea. J Infect Dis. 1984 Feb;149(2):166–174. doi: 10.1093/infdis/149.2.166. [DOI] [PubMed] [Google Scholar]
  135. Zhang Q. Y., DeRyckere D., Lauer P., Koomey M. Gene conversion in Neisseria gonorrhoeae: evidence for its role in pilus antigenic variation. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5366–5370. doi: 10.1073/pnas.89.12.5366. [DOI] [PMC free article] [PubMed] [Google Scholar]
  136. van Putten J. P. Phase variation of lipopolysaccharide directs interconversion of invasive and immuno-resistant phenotypes of Neisseria gonorrhoeae. EMBO J. 1993 Nov;12(11):4043–4051. doi: 10.1002/j.1460-2075.1993.tb06088.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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