1887

Abstract

Pilus-mediated adherence to mucosal epithelial cells is a critical step for to establish an infection in the human host. CD46, the defined receptor for the gonococcal pilus, is a complement-regulatory protein that is expressed on all human nucleated cells. It was observed that a piliated, Opa variant of gonococcal strain FA1090 adhered with different efficiencies to the human epithelial cell lines tested (Chang, ME180, HEC-1B and PC-3). Surprisingly, these differences in adherence levels did not correlate with levels of CD46 expressed by these cell lines. In fact, there was an inverse relationship between total surface-exposed CD46 and gonococcal adherence. Four major isoforms of CD46 are produced due to alternative RNA splicing of a surface-exposed region and the cytoplasmic tail. The relative isoform surface expression of each cell line was determined, and each was found to express different ratios of the four CD46 isoforms. No correlation could be derived between CD46 isoform surface expression and pilus-mediated gonococcal adherence, indicating that CD46 does not act as a classic receptor for gonococcal pili.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-147-8-2333
2001-08-01
2024-04-16
Loading full text...

Full text loading...

/deliver/fulltext/micro/147/8/1472333a.html?itemId=/content/journal/micro/10.1099/00221287-147-8-2333&mimeType=html&fmt=ahah

References

  1. Chen T., Belland R. J., Wilson J., Swanson J. 1995; Adherence of pilus- Opa+ gonococci to epithelial cells in vitro involves heparan sulfate. J Exp Med 182:511–517 [CrossRef]
    [Google Scholar]
  2. Dorig R. E., Marcil A., Chopra A., Richardson C. D. 1993; The human CD46 molecule is a receptor for measles virus (Edmonston strain). Cell 75:295–305 [CrossRef]
    [Google Scholar]
  3. Handsfield H. H., Hodson W. A., Holmes K. K. 1973; Neonatal gonococcal infection. I. Orogastric contamination with Neisseria gonorrhoeae. JAMA (J Am Med Assoc) 225:697–701
    [Google Scholar]
  4. Johnstone R. W., Loveland B. E., McKenzie I. F. 1993; Identification and quantification of complement regulator CD46 on normal human tissues. Immunol 79:341–347
    [Google Scholar]
  5. Jonsson A. B., Nyberg G., Normark S. 1991; Phase variation of gonococcal pili by frameshift mutation in pilC , a novel gene for pilus assembly. EMBO J 10:477–488
    [Google Scholar]
  6. Jonsson A. B., Ilver D., Falk P., Pepose J., Normark S. 1994; Sequence changes in the pilus subunit lead to tropism variation of Neisseria gonorrhoeae to human tissue. Mol Microbiol 13:403–416 [CrossRef]
    [Google Scholar]
  7. Källström H., Liszewski M. K., Atkinson J. P., Jonsson A. B. 1997; Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria . Mol Microbiol 25:639–647 [CrossRef]
    [Google Scholar]
  8. Källström H., Islam M. S., Berggren P. O., Jonsson A. B. 1998; Cell signaling by the type IV pili of pathogenic Neisseria . J Biol Chem 273:21777–21782 [CrossRef]
    [Google Scholar]
  9. Källström H., Blackmer Gill D., Albiger B., Liszewski M. K., Atkinson J. P., Jonsson A. B. 2001; Attachment of Neisseria gonorrhoeae to the cellular pilus receptor CD46: identification of domains important for bacterial adherence. Cell Microbiol 3:133–143 [CrossRef]
    [Google Scholar]
  10. Karp C. L., Wysocka M., Wahl L. M., Ahearn J. M., Cuomo P. J., Sherry B., Trinchieri G., Griffin D. E. 1996; Mechanism of suppression of cell-mediated immunity by measles virus. Science 273:228–231 erratum Science 275, 1053
    [Google Scholar]
  11. Kellogg D. S. Jr, Peacock W. L., Deacon W. E., Brown L., Pirkle C. I. 1963; Neisseria gonorrhoeae . I. Virulence genetically linked to clonal variation. J Bacteriol 85:1274–1279
    [Google Scholar]
  12. Koomey J. M., Falkow S. 1987; Cloning of the recA gene of Neisseria gonorrhoeae and construction of gonococcal recA mutants. J Bacteriol 169:790–795
    [Google Scholar]
  13. Liszewski M. K., Post T. W., Atkinson J. P. 1991; Membrane cofactor protein (MCP or CD46): newest member of the regulators of complement activation gene cluster. Annu Rev Immunol 9:431–455 [CrossRef]
    [Google Scholar]
  14. Logan R. P., Robins A., Turner G. A., Cockayne A., Borriello S. P., Hawkey C. J. 1998; A novel flow cytometric assay for quantitating adherence of Helicobacter pylori to gastric epithelial cells. J Immunol Methods 213:19–30 [CrossRef]
    [Google Scholar]
  15. Long C. D., Madraswala R. N., Seifert H. S. 1998; Comparisons between colony phase variation of Neisseria gonorrhoeae FA1090 and pilus, pilin, and S-pilin expression. Infect Immun 66:1918–1927
    [Google Scholar]
  16. McNearney T., Ballard L., Seya T., Atkinson J. P. 1989; Membrane cofactor protein of complement is present on human fibroblast, epithelial, and endothelial cells. J Clin Invest 84:538–545 [CrossRef]
    [Google Scholar]
  17. Merz A. J., Rifenbery D. B., Arvidson C. G., So M. 1996; Traversal of a polarized epithelium by pathogenic Neisseriae : facilitation by type IV pili and maintenance of epithelial barrier function. Mol Med 2:745–754
    [Google Scholar]
  18. Nassif X., So M. 1995; Interaction of pathogenic neisseriae with nonphagocytic cells. Clin Microbiol Rev 8:376–388
    [Google Scholar]
  19. Nassif X., Pujol C., Morand P., Eugene E. 1999; Interactions of pathogenic Neisseria with host cells. Is it possible to assemble the puzzle?. Mol Microbiol 32:1124–1132 [CrossRef]
    [Google Scholar]
  20. Okada N., Liszewski M. K., Atkinson J. P., Caparon M. 1995; Membrane cofactor protein (CD46) is a keratinocyte receptor for the M protein of the group A streptococcus. Proc Natl Acad Sci USA 92:2489–2493 [CrossRef]
    [Google Scholar]
  21. Porat N., Apicella M. A., Blake M. S. 1995; Neisseria gonorrhoeae utilizes and enhances the biosynthesis of the asialoglycoprotein receptor expressed on the surface of the hepatic HepG2 cell line. Infect Immun 63:1498–1506
    [Google Scholar]
  22. Post T. W., Liszewski M. K., Adams E. M., Tedja I., Miller E. A., Atkinson J. P. 1991; Membrane cofactor protein of the complement system: alternative splicing of serine/threonine/proline-rich exons and cytoplasmic tails produces multiple isoforms that correlate with protein phenotype. J Exp Med 174:93–102 [CrossRef]
    [Google Scholar]
  23. Rahman M., Normark S., Jonsson A. B., Källström H. 1997; PilC of pathogenic Neisseria is associated with the bacterial cell surface. Mol Microbiol 25:11–25 [CrossRef]
    [Google Scholar]
  24. Rudel T., Gibbs C. P., Haas R., Meyer T. F., van Putten J. P. 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 [CrossRef]
    [Google Scholar]
  25. Rudel T., Scheurerpflug I., Meyer T. F. 1995; Neisseria PilC protein identified as type-4 pilus tip-located adhesin. Nature 373:357–359 [CrossRef]
    [Google Scholar]
  26. Russell S. M., Sparrow R. L., McKenzie I. F., Purcell D. F. 1992; Tissue-specific and allelic expression of the complement regulator CD46 is controlled by alternative splicing. Eur J Immunol 22:1513–1518 [CrossRef]
    [Google Scholar]
  27. Santoro F., Kennedy P. E., Locatelli G., Malnati M. S., Berger E. A., Lusso P. 1999; CD46 is a cellular receptor for human herpesvirus 6. Cell 99:817–827 [CrossRef]
    [Google Scholar]
  28. Sasaki M., Joh T., Tada T., Okada N., Yokoyama Y., Itoh M. 1998; Altered expression of membrane inhibitors of complement in human gastric epithelium during Helicobacter -associated gastritis. Histopathology 33:554–560 [CrossRef]
    [Google Scholar]
  29. Scheuerpflug I., Rudel T., Ryll R., Pandit J., Meyer T. F. 1999; 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
    [Google Scholar]
  30. Seifert H. S. 1997; Insertionally inactivated and inducible recA alleles for use in Neisseria . Gene 188:215–220 [CrossRef]
    [Google Scholar]
  31. Seya T., Turner J. R., Atkinson J. P. 1986; Purification and characterization of a membrane protein (gp45-70) that is a cofactor for cleavage of C3b and C4b. J Exp Med 163:837–855 [CrossRef]
    [Google Scholar]
  32. Seya T., Hara T., Matsumoto M., Akedo H. 1990; Quantitative analysis of membrane cofactor protein (MCP) of complement. High expression of MCP on human leukemia cell lines, which is down-regulated during cell differentiation. J Immunol 145:238–245
    [Google Scholar]
  33. Swanson J., Robbins K., Barrera O., Corwin D., Boslego J., Ciak J., Blake M., Koomey J. M. 1987; Gonococcal pilin variants in experimental gonorrhea. J Exp Med 165:1344–1357 [CrossRef]
    [Google Scholar]
  34. Virji M., Makepeace K., Ferguson D. J., Watt S. M. 1996a; Carcinoembryonic antigens (CD66) on epithelial cells and neutrophils are receptors for Opa proteins of pathogenic neisseriae. Mol Microbiol 22:941–950 [CrossRef]
    [Google Scholar]
  35. Virji M., Watt S. M., Barker S., Makepeace K., Doyonnas R. 1996b; 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 [CrossRef]
    [Google Scholar]
  36. Wang G., Liszewski M. K., Chan A. C., Atkinson J. P. 2000; Membrane cofactor protein (MCP; CD46): isoform-specific tyrosine phosphorylation. J Immunol 164:1839–1846 [CrossRef]
    [Google Scholar]
  37. Weston S. A., Parish C. R. 1990; New fluorescent dyes for lymphocyte migration studies. Analysis by flow cytometry and fluorescence microscopy. J Immunol Methods 133:87–97 [CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-147-8-2333
Loading
/content/journal/micro/10.1099/00221287-147-8-2333
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error