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Mol Med. 1996 November; 2(6): 745–754.
PMCID: PMC2230138

Traversal of a polarized epithelium by pathogenic Neisseriae: facilitation by type IV pili and maintenance of epithelial barrier function.

Abstract

BACKGROUND: Gonococci (GC) and meningococci (MC) are gram-negative bacterial pathogens that infect human mucosal epithelia. We would like to understand the functions of specific bacterial components at each stage of mucosal colonization: adhesion, cell invasion, and traversal into subepithelial tissues. As no animal model of mucosal colonization by GC or MC is available, increasingly sophisticated in vitro approaches have been used to address these issues. MATERIALS AND METHODS: We adapted the polarized T84 human epithelial cell system to study GC and MC colonization. Epithelial barrier function was monitored by permeability to soluble tracers and with electrical resistance measurements. Polarized cells were used to assay bacterial traversal of the monolayers, and cells grown on plastic were used to assay adhesion and cell invasion. RESULTS: All pathogenic Neisseriae examined traversed the monolayers. The traversal times were species specific and identical to times established previously in organ culture studies. In contrast to experiments with some enteric pathogens, transmigration by GC and MC was not accompanied by disruption of the epithelial barrier. GC mutants lacking type IV pili were compromised in adhesion, invasion, and traversal of T84 cells. CONCLUSIONS: Experiments with polarized T84 cells mimic key features of organ culture infections and reveal additional aspects of neisserial infection. Epithelial barrier function can be retained during bacterial traversal. Experiments with a nonpiliated GC mutant and its wild-type parent indicated an unexpected role for pili in cell invasion. Our results are consistent with the hypothesis that bacterial adhesion, invasion, or both are rate-limiting for traversal across the epithelium.

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Selected References

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  • Cohen MS, Sparling PF. Mucosal infection with Neisseria gonorrhoeae. Bacterial adaptation and mucosal defenses. J Clin Invest. 1992 Jun;89(6):1699–1705. [PMC free article] [PubMed]
  • Nassif X, So M. Interaction of pathogenic neisseriae with nonphagocytic cells. Clin Microbiol Rev. 1995 Jul;8(3):376–388. [PMC free article] [PubMed]
  • Laga M, Manoka A, Kivuvu M, Malele B, Tuliza M, Nzila N, Goeman J, Behets F, Batter V, Alary M, et al. Non-ulcerative sexually transmitted diseases as risk factors for HIV-1 transmission in women: results from a cohort study. AIDS. 1993 Jan;7(1):95–102. [PubMed]
  • Weir SS, Feldblum PJ, Roddy RE, Zekeng L. Gonorrhea as a risk factor for HIV acquisition. AIDS. 1994 Nov;8(11):1605–1608. [PubMed]
  • McGee ZA, Stephens DS, Hoffman LH, Schlech WF, 3rd, Horn RG. Mechanisms of mucosal invasion by pathogenic Neisseria. Rev Infect Dis. 1983 Sep-Oct;5 (Suppl 4):S708–S714. [PubMed]
  • Stephens DS, Farley MM. Pathogenic events during infection of the human nasopharynx with Neisseria meningitidis and Haemophilus influenzae. Rev Infect Dis. 1991 Jan-Feb;13(1):22–33. [PubMed]
  • Silverstein SC, Steinman RM, Cohn ZA. Endocytosis. Annu Rev Biochem. 1977;46:669–722. [PubMed]
  • Shaw JH, Falkow S. Model for invasion of human tissue culture cells by Neisseria gonorrhoeae. Infect Immun. 1988 Jun;56(6):1625–1632. [PMC free article] [PubMed]
  • Chen JC, Bavoil P, Clark VL. 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. [PubMed]
  • Cohen MS, Cannon JG, Jerse AE, Charniga LM, Isbey SF, Whicker LG. 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. [PubMed]
  • Bessen D, Gotschlich EC. Interactions of gonococci with HeLa cells: attachment, detachment, replication, penetration, and the role of protein II. Infect Immun. 1986 Oct;54(1):154–160. [PMC free article] [PubMed]
  • Weel JF, Hopman CT, van Putten JP. 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. [PMC free article] [PubMed]
  • van Putten JP. Phase variation of lipopolysaccharide directs interconversion of invasive and immuno-resistant phenotypes of Neisseria gonorrhoeae. EMBO J. 1993 Nov;12(11):4043–4051. [PubMed]
  • 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. [PubMed]
  • Virji M, Kayhty H, Ferguson DJ, Alexandrescu C, Heckels JE, Moxon ER. The role of pili in the interactions of pathogenic Neisseria with cultured human endothelial cells. Mol Microbiol. 1991 Aug;5(8):1831–1841. [PubMed]
  • Virji M, Makepeace K, Moxon ER. 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. 1994 Oct;14(1):173–184. [PubMed]
  • GROBSTEIN C. Trans-filter induction of tubules in mouse metanephrogenic mesenchyme. Exp Cell Res. 1956 Apr;10(2):424–440. [PubMed]
  • Cereijido M, Robbins ES, Dolan WJ, Rotunno CA, Sabatini DD. Polarized monolayers formed by epithelial cells on a permeable and translucent support. J Cell Biol. 1978 Jun;77(3):853–880. [PMC free article] [PubMed]
  • Mostov KE, Deitcher DL. Polymeric immunoglobulin receptor expressed in MDCK cells transcytoses IgA. Cell. 1986 Aug 15;46(4):613–621. [PubMed]
  • Rodriguez Boulan E, Pendergast M. Polarized distribution of viral envelope proteins in the plasma membrane of infected epithelial cells. Cell. 1980 May;20(1):45–54. [PubMed]
  • Dharmsathaphorn K, Madara JL. Established intestinal cell lines as model systems for electrolyte transport studies. Methods Enzymol. 1990;192:354–389. [PubMed]
  • Finlay BB, Gumbiner B, Falkow S. Penetration of Salmonella through a polarized Madin-Darby canine kidney epithelial cell monolayer. J Cell Biol. 1988 Jul;107(1):221–230. [PMC free article] [PubMed]
  • Finlay BB, Falkow S. Salmonella interactions with polarized human intestinal Caco-2 epithelial cells. J Infect Dis. 1990 Nov;162(5):1096–1106. [PubMed]
  • McCormick BA, Hofman PM, Kim J, Carnes DK, Miller SI, Madara JL. Surface attachment of Salmonella typhimurium to intestinal epithelia imprints the subepithelial matrix with gradients chemotactic for neutrophils. J Cell Biol. 1995 Dec;131(6 Pt 1):1599–1608. [PMC free article] [PubMed]
  • Birkness KA, Swisher BL, White EH, Long EG, Ewing EP, Jr, Quinn FD. A tissue culture bilayer model to study the passage of Neisseria meningitidis. Infect Immun. 1995 Feb;63(2):402–409. [PMC free article] [PubMed]
  • Canil C, Rosenshine I, Ruschkowski S, Donnenberg MS, Kaper JB, Finlay BB. Enteropathogenic Escherichia coli decreases the transepithelial electrical resistance of polarized epithelial monolayers. Infect Immun. 1993 Jul;61(7):2755–2762. [PMC free article] [PubMed]
  • Jepson MA, Collares-Buzato CB, Clark MA, Hirst BH, Simmons NL. Rapid disruption of epithelial barrier function by Salmonella typhimurium is associated with structural modification of intercellular junctions. Infect Immun. 1995 Jan;63(1):356–359. [PMC free article] [PubMed]
  • Segal E, Billyard E, So M, Storzbach S, Meyer TF. Role of chromosomal rearrangement in N. gonorrhoeae pilus phase variation. Cell. 1985 Feb;40(2):293–300. [PubMed]
  • Trieu-Cuot P, Poyart-Salmeron C, Carlier C, Courvalin P. Nucleotide sequence of the erythromycin resistance gene of the conjugative transposon Tn1545. Nucleic Acids Res. 1990 Jun 25;18(12):3660–3660. [PMC free article] [PubMed]
  • Waldbeser LS, Ajioka RS, Merz AJ, 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. [PubMed]
  • Sparling PF. Genetic transformation of Neisseria gonorrhoeae to streptomycin resistance. J Bacteriol. 1966 Nov;92(5):1364–1371. [PMC free article] [PubMed]
  • Rochat T, Casale J, Hunninghake GW, Peterson MW. Neutrophil cathepsin G increases permeability of cultured type II pneumocytes. Am J Physiol. 1988 Nov;255(5 Pt 1):C603–C611. [PubMed]
  • Stephens DS, Hoffman LH, McGee ZA. Interaction of Neisseria meningitidis with human nasopharyngeal mucosa: attachment and entry into columnar epithelial cells. J Infect Dis. 1983 Sep;148(3):369–376. [PubMed]
  • McGee ZA, Johnson AP, 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. [PubMed]
  • Schmidt A, Heid HW, Schäfer S, Nuber UA, Zimbelmann R, Franke WW. Desmosomes and cytoskeletal architecture in epithelial differentiation: cell type-specific plaque components and intermediate filament anchorage. Eur J Cell Biol. 1994 Dec;65(2):229–245. [PubMed]
  • KELLOGG DS, Jr, PEACOCK WL, Jr, DEACON WE, BROWN L, PIRKLE DI. NEISSERIA GONORRHOEAE. I. VIRULENCE GENETICALLY LINKED TO CLONAL VARIATION. J Bacteriol. 1963 Jun;85:1274–1279. [PMC free article] [PubMed]
  • Swanson J, Barrera O, Sola J, Boslego J. Expression of outer membrane protein II by gonococci in experimental gonorrhea. J Exp Med. 1988 Dec 1;168(6):2121–2129. [PMC free article] [PubMed]
  • 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. [PMC free article] [PubMed]
  • Makino S, van Putten JP, Meyer TF. 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. [PubMed]

Articles from Molecular Medicine are provided here courtesy of The Feinstein Institute for Medical Research at North Shore LIJ