Chapter 11 : Gender Differences in Pathogenesis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Gender Differences in Pathogenesis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555815851/9781555814694_Chap11-1.gif /docserver/preview/fulltext/10.1128/9781555815851/9781555814694_Chap11-2.gif


Today, infections attributed to continue to be a national and international problem, despite the fact that antibiotic therapy is available. This chapter attempts to contrast the different mechanisms of pathogenesis used by to infect, to invade, and to colonize the mucosal epithelia of the urethra and the uterine cervix, the initial sites of infection in males and females, respectively. Included among the better-studied outer membrane gonococcal constituents contributing to its virulence are pili, porin, the opacity-associated (Opa) outer membrane proteins, and lipooligosaccharide (LOS). Work by many researchers has revealed additional factors that may contribute to virulence; however, the roles of these factors in human disease are less well defined than those described for pili, porin, Opa proteins, and LOS. Before the 1970s, the understanding of gonococcal pathogenesis in the lower female genital tract was based on light microscopy studies performed by Harkness in the 1940s. The male urethra and the female uterine cervix, the primary sites of the majority of gonococcal infections, are distinctly different epithelial cell surfaces, which result from different embryological origins. While the importance of virulence factors such as pili, porin, Opa, and LOS in gonococcal infection both in vitro and in vivo is well established, the contribution of other virulence factors is undetermined or requires further elucidation.

Citation: Edwards J. 2007. Gender Differences in Pathogenesis, p 149-173. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch11

Key Concept Ranking

Human immunodeficiency virus 1
Tumor Necrosis Factor alpha
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of FIGURE 1

The intimate association of gonococcal and male urethral epithelial cell membranes is visible in both panels. (A) Transmission electron micrograph of a urethral epithelial cell within a urethral exudate obtained from a man with naturally acquired gonococcal urethritis. Gonococci are denoted by arrows. Note the tight vacuole surrounding the intracellular organism (large arrow). (B) Scanning electron micrograph of primary male urethral epithelial cells after infection with gonococci. Magnification: panel A, ×23,000; panel B, ×40,000. Reprinted from ( ).

Citation: Edwards J. 2007. Gender Differences in Pathogenesis, p 149-173. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of FIGURE 2

Electron microscopy demonstrates that membrane ruffling and macropinocytosis occur upon cervical infection in vitro and in vivo. (A) Scanning electron micrograph of a membrane ruffle after a 90-min infection of primary cervical epithelial cells. Arrows highlight a gonococcus cell engulfed within membrane folds of the ruffle. (B to D) Transmission electron micrographs revealing large membrane protrusions (small arrows) and the presence of gonococci in spacious vacuoles (large arrows), suggestive of membrane ruffling and macropinocytosis, respectively. (B) Gonococcal infection of primary cervical epithelial cells results in gonococcus internalization within spacious, actin-lined vacuoles. (C and D) Large membrane protrusions engulf gonococci in a clinical biopsy sample obtained from a woman with culture-documented gonococcal cervicitis (C) and in a culture of primary cervical epithelial cells 3 h postinfection (D). Magnification: panel A, ×11,000; panel B, ×22,000; panels C and D, ×40,000. Panels A and C are reprinted from ( ) and panels B and D are reprinted from ( ).

Citation: Edwards J. 2007. Gender Differences in Pathogenesis, p 149-173. In Brogden K, Minion F, Cornick N, Stanton T, Zhang Q, Nolan L, Wannemuehler M (ed), Virulence Mechanisms of Bacterial Pathogens, Fourth Edition. ASM Press, Washington, DC. doi: 10.1128/9781555815851.ch11
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Al-Suleiman, S. A.,, E. M. Grimes, and, H. S. Jonas. 1983. Disseminated gonococcal infections. Obstet. Gynecol. 61:4851.
2. Apicella, M. A.,, M. Ketterer,, F. K. Lee,, D. Zhou,, P. A. Rice, and, M. S. Blake. 1996. The pathogenesis of gonococcal urethritis in men: confocal and immunoelectron microscopic analysis of urethral exudates from men infected with Neisseria gonorrhoeae. J. Infect. Dis. 173:636646.
3. Apicella, M. A.,, R. E. Mandrell,, M. Shero,, M. E. Wilson,, J. M. Griffiss,, G. F. Brooks,, C. Lammel,, J. F. Breen, and, P. A. Rice. 1990. Modification by sialic acid of Neisseria gonorrhoeae lipooligosaccharide epitope expression in human urethral exudates: an immunoelectron microscopic analysis. J. Infect. Dis. 162:506512.
4. Apicella, M. A.,, M. Shero,, G. A. Jarvis,, J. M. Griffiss,, R. E. Mandrell, and, H. Schneider. 1987. Phenotypic variation in epitope expression of the Neisseria gonorrhoeae lipooligosaccharide. Infect. Immun. 55:17551761.
5. Aral, S. O.,, W. D. Mosher, and, W. Cates. 1991. Self-reported pelvic inflammatory disease in the United States. JAMA 266:25702573.
6. Arko, R. J. 1972. Neisseria gonorrhoeae: experimental infection of laboratory animals. Science 177:200201.
7. Arko, R. J. 1989. Animal models for pathogenic Neisseria species. Clin. Microbiol. Rev. 2:S56S59.
8. Ayala, P.,, L. Lin,, S. Hopper,, M. Fukuda, and, M. So. 1998. Infection of epithelial cells by pathogenic neisseriae reduces the levels of multiple lysosomal constituents. Infect. Immun. 66:50015007.
9. Berton, G.,, C. Laudanna,, C. Sorio, and, F. Rossi. 1992. Generation of signals activating neutrophil functions by leukocyte integrins: LFA-1 and gp150/95, but not CR3, are able to stimulate the respiratory burst of human neutrophils. J. Cell Biol. 116:10071017.
10. Binnicker, M. J.,, R. D. Williams, and, M. A. Apicella. 2003. Infection of human urethral epithelium with Neisseria gonorrhoeae elicits an up-regulation of host antiapoptotic factors and protects cells from staurosporin-induced apoptosis. Cell. Microbiol. 5:549560.
11. Binnicker, M. J.,, R. D. Williams, and, M. A. Apicella. 2004. Gonococcal porin IB activates NF-κB in human urethral epithelium and increases the expression of host antiapoptotic factors. Infect. Immun. 72:64086417.
12. Biswas, G. D., and, P. F. Sparling. 1995. Characterization of lbpA, the structural gene for a lactoferrin receptor in Neisseria gonorrhoeae. Infect. Immun. 63:29582967.
13. Bjerknes, R.,, H.-K. Guttormsen,, C. O. Solberg, and, L. M. Wetzler. 1995. Neisserial porins inhibit human neutrophil actin polymerization, degranulation, opsonin receptor expression, and phagocytosis but prime the neutrophils to increase their oxidative burst. Infect. Immun. 63:160167.
14. Blake, M. S. 1985. Implications of the active role of gonococcal porins in disease, p. 251258. In G. K. Schoolnik (ed.), The Pathogenic Neisseriae: Proceedings of the Fourth International Symposium. ASM Press, Washington, DC.
15. Blake, M. S., and, E. C. Gotschlich. 1987. Functional and immunological properties of pathogenic Neisseria surface proteins, p. 377400. In M. Inouye (ed.), Bacterial Outer Membranes as Model Systems. John Wiley and Sons, New York, NY.
16. Bolan, G.,, A. A. Ehrhardt, and, J. N. Wasserheit. 1999. Gender perspectives and STDs, p. 117127. In K. K. Holmes,, P.-A. Mardh,, P. F. Sparling,, S. M. Lemon,, W. E. Stamm,, P. Piot, and, J. N. Wasserheit (ed.), Sexually Transmitted Diseases, 3rd ed. McGraw-Hill, New York, NY.
17. Bos, M. P.,, F. Grunert, and, R. J. Belland. 1997. Differential recognition of members of the carcinoembryonic antigen family by Opa variants of Neisseria gonorrhoeae. Infect. Immun. 65:23532361.
18. Boulton, I. C., and, S. D. Gray-Owen. 2002. Neisserial binding to CEACAM1 arrests the activation and proliferation of CD4+ T lymphocytes. Nat. Immunol. 3:229236.
19. Brodeur, B. R.,, W. M. Johnson,, K. G. Johnson, and, B. B. Diena. 1977. In vitro interaction of Neisseria gonorrhoeae type 1 and type 4 with tissue culture cells. Infect. Immun. 15:560567.
20. Burch, C. L.,, R. J. Danaher, and, D. C. Stein. 1997. Antigenic variation in Neisseria gonorrhoeae: production of multiple lipooligosaccharides. J. Bacteriol. 179:982986.
21. Campagnari, A. A.,, S. M. Spinola,, A. J. Lesse,, Y. A. Kwaik,, R. E. Mandrell, and, M. A. Apicella. 1990. Lipooligosaccharide epitopes shared among gram-negative non-enteric mucosal pathogens. Microb. Pathog. 8:353362.
22. Cardinale, J. A., and, V. L. Clark. 2005. Determinants of nitric oxide steady-state levels during anaerobic respiration by Neisseria gonorrhoeae. Mol. Microbiol. 58:177188.
23. Cardinale, J. A., and, V. L. Clark. 2000. Expression of AniA, the major anaerobically induced outer membrane protein of Neisseria gonorrhoeae, provides protection against killing by normal human sera. Infect. Immun. 68:43684369.
24. Carney, F. E., Jr., and, D. Taylor-Robinson. 1973. Growth and effect of Neisseria gonorrhoeae in organ cultures. Br. J. Vener. Dis. 49:435440.
25. Caron, E., and, A. Hall. 1998. Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases. Science 282:17171720.
26. Carson, S. D.,, P. E. Klebba,, S. M. Newton, and, P. F. Sparling. 1999. Ferric enterobactin binding and utilization by Neisseria gonorrhoeae. J. Bacteriol. 181:28952901.
27. Casey, S. G.,, W. M. Shafer, and, J. K. Spitznagel. 1986. Neisseria gonorrhoeae survives intraleukocytic oxygen-independent antimicrobial capacities of anaerobic and aerobic granulocytes in the presence of pyocin lethal for extracellular gonococci. Infect. Immun. 52:384389.
28. Casey, S. G.,, W. M. Shafer, and, J. K. Spitznagel. 1985. Anaerobiosis increases resistance of Neisseria gonorrhoeae to O2-independent antimicrobial proteins from human polymorphonuclear granulocytes. Infect. Immun. 47:401407.
29. Casey, S. G.,, D. R. Veale, and, H. Smith. 1979. Demonstration of intracellular growth of gonococci in human phagocytes using spectinomycin to kill extracellular organisms. J. Gen. Microbiol. 113:395398.
30. Chen, A.,, I. C. Boulton,, J. Pongoski,, A. Cochrane, and, S. D. Gray-Owen. 2003. Induction of HIV-1 long terminal repeat-mediated transcription by Neisseria gonorrhoeae. AIDS 17:625628.
31. Chen, C.,, D. M. Tobiason,, C. E. Thomas,, W. M. Shafer,, H. S. Seifert, and, P. F. Sparling. 2004. A mutant form of the Neisseria gonorrhoeae pilus secretin protein PilQ allows increased entry of heme and antimicrobial peptides. J. Bacteriol. 186:730739.
32. Chen, C.-J.,, P. F. Sparling,, L. A. Lewis,, D. W. Dyer, and, C. Elkins. 1996. Identification and purification of a hemoglobin-binding outer membrane protein from Neisseria gonorrhoeae. Infect. Immun. 64:50085014.
33. Chen, C.-Y.,, C. A. Genco,, J. P. Rock, and, S. A. Morse. 1989. Physiology and metabolism of Neisseria gonorrhoeae and Neisseria meningitidis: implications for pathogenesis. Clin. Microbiol. Rev. 2:S35S40.
34. Chen, J. C.-R.,, P. Bavoil, and, V. L. Clark. 1991. Enhancement of the invasive ability of Neisseria gonorrhoeae by contact with HecIB, an adenocarcinoma endometrial cell line. Mol. Microbiol. 5:15311538.
35. Chen, T.,, S. Bolland,, I. Chen,, J. Parker,, M. Pantelic,, F. Grunert, and, W. Zimmermann. 2001. The CGM1a (CEACAM3/CD66d)-mediated phagocytic pathway of Neisseria gonorrhoeae expressing opacity proteins is also the pathway to cell death. J. Biol. Chem. 276:1741317419.
36. Clark, V. L.,, L. A. Campbell,, D. A. Palermo,, T. M. Evans, and, K. W. Klimpel. 1987. Induction and repression of outer membrane proteins by anaerobic growth of Neisseria gonorrhoeae. Infect. Immun. 55:13591364.
37. Clark, V. L.,, J. S. Knapp,, S. Thompson, and, K. W. Klimpel. 1988. Presence of antibodies to the major anaerobically induced gonococcal outer membrane protein in sera from patients with gonococcal infections. Microb. Pathog. 5:381390.
38. Cohen, M. S.,, J. G. Cannon,, A. E. Jerse,, L. M. Charniga,, S. F. Isbey, and, L. G. Whicker. 1994. Human experimentation with Neisseria gonorrhoeae: rationale, methods, and implications for the biology of infection and vaccine development. J. Infect. Dis. 169:532537.
39. Cornelissen, C. N.,, J. E. Anderson,, I. C. Boulton, and, P. F. Sparling. 2000. Antigenic and sequence diversity in gonococcal transferrin-binding protein A. Infect. Immun. 68:47254735.
40. Cornelissen, C. N.,, J. E. Anderson, and, P. F. Sparling. 1997. Characterization of the diversity and the transferrin-binding domain of gonococcal transferrin-binding protein 2. Infect. Immun. 65:822828.
41. Cornelissen, C. N.,, M. Kelley,, M. M. Hobbs,, J. E. Anderson,, J. G. Cannon,, M. S. Cohen, and, P. F. Sparling. 1998. The transferrin receptor expressed by gonococcal strain FA1090 is required for experimental infection of human male volunteers. Mol. Microbiol. 27:611616.
42. Danaher, R. J.,, J. C. Levin,, D. Arking,, C. L. Burch,, R. Sandlin, and, D. C. Stein. 1995. Genetic basis of Neisseria gonorrhoeae lipooligosaccharide antigenic variation. J. Bacteriol. 177:72757279.
43. Darmon, M.,, C. Delescluse,, A. Semat,, B. Bernard,, J. Bailly, and, M. Prunieras. 1984. A keratin of fetal skin is reexpressed in human keratinocytes transformed by SV40 virus or treated with the tumor promoter TPA. Exp. Cell Res. 154:315319.
44. Dehio, C.,, S. D. Gray-Owen, and, T. F. Meyer. 2000. Host cell invasion by pathogenic Neisseriae, p. 6196. In T. A. Oelschlaeger and, J. Hacker (ed.), Subcellular Biochemistry, vol. 33. Bacterial Invasion into Eukaryotic Cells. Plenum Publishers, New York, NY.
45. Demarco de Hormaeche, R.,, H. Jessop, and, K. Senior. 1988. Gonococcal variants selected by growth in vivo or in vitro have antigenically different LPS. Microb. Pathog. 4:289297.
46. Densen, P. 1989. Interaction of complement with Neisseria meningitidis and Neisseria gonorrhoeae. Clin. Microbiol. Rev. 2:S11S17.
47. Densen, P.,, L. A. MacKeen, and, R. A. Clark. 1982. Dissemination of gonococcal infection is associated with delayed stimulation of complement-dependent neutrophil chemotaxis in vitro. Infect. Immun. 38:563572.
48. Densen, P., and, G. L. Mandell. 1978. Gonococcal interactions with polymorphonuclear neutrophils: importance of the phagosome for bactericidal activity. J. Clin. Investig. 62:11611171.
49. Desai, P. J.,, R. Nzeribe, and, C. A. Genco. 1995. Binding and accumulation of hemin in Neisseria gonorrhoeae. Infect. Immun. 63:46344641.
50. Dillard, J. P., and, H. S. Seifert. 1997. A peptidoglycan hydrolase similar to bacteriophage endolysin acts as an autolysin in Neisseria gonorrhoeae. Mol. Microbiol. 25:893901.
51. Dini, L.,, L. Falasca,, A. Lentini,, P. Mattioli,, M. Piacentini,, L. Piredda, and, F. Autuori. 1993. Galactose-specific receptor modulation related to the onset of apoptosis in rat liver. Eur. J. Cell Biol. 61:329337.
52. DiPaolo, J. A.,, N. C. Popescu,, L. Alvarez, and, C. D. Woodworth. 1993. Cellular and molecular alterations in human epithelial cells transformed by recombinant human papillomavirus DNA. Crit. Rev. Oncog. 4:337360.
53. Duensing, T. D., and, J. P. M. van Putten. 1997. Vitronectin binds to the gonococcal adhesin OpaA through a glycoaminoglycan molecular bridge. Biochem. J. 334:133139.
54. Dunn, K. L. R.,, M. Virji, and, E. R. Moxon. 1995. Investigations into the molecular basis of meningococcal toxicity for human endothelial and epithelial cells: the synergistic effect of LPS and pili. Microb. Pathog. 18:8196.
55. Dyer, D. W.,, E. P. West, and, P. F. Sparling. 1987. Effects of serum carrier proteins on the growth of pathogenic neisseriae with heme-bound iron. Infect. Immun. 55:21712175.
56. Edwards, J. L., and, M. A. Apicella. 2002. The role of lipooligosaccharide in Neisseria gonorrhoeae pathogenesis of cervical epithelia: lipid A serves as a C3 acceptor molecule. Cell. Microbiol. 4:585598.
57. Edwards, J. L., and, M. A. Apicella. 2004. The molecular mechanisms used by Neisseria gonorrhoeae to initiate infection differ between men and women. Clin. Microbiol. Rev. 17:965981.
58. Edwards, J. L., and, M. A. Apicella. 2005. I-domain-containing integrins serve as pilus receptors for Neisseria gonorrhoeae adherence to human epithelial cells. Cell. Microbiol. 7:11971211.
59. Edwards, J. L., and, M. A. Apicella. 2006. Gonococcal PLD directly interacts with Akt kinase upon infection of primary human cervical epithelial cells. Cell. Microbiol. 8:12531271.
60. Edwards, J. L.,, E. J. Brown,, S. Uk-Nham,, J. G. Cannon,, M. S. Blake, and, M. A. Apicella. 2002. A co-operative interaction between Neisseria gonorrhoeae and complement receptor 3 mediates infection of primary cervical epithelial cells. Cell. Microbiol. 4:571584.
61. Edwards, J. L.,, E. J. Brown,, K. A. Ault, and, M. A. Apicella. 2001. The role of complement receptor 3 (CR3) in Neisseria gonorrhoeae infection of human cervical epithelia. Cell. Microbiol. 3:611622.
62. Edwards, J. L.,, D. D. Entz, and, M. A. Apicella. 2003. Gonococcal phospholipase D modulates the expression and function of complement receptor 3 in primary cervical epithelial cells. Infect. Immun. 71:63816391.
63. Edwards, J. L.,, J. Q. Shao,, K. A. Ault, and, M. A. Apicella. 2000. Neisseria gonorrhoeae elicits membrane ruffling and cytoskeletal rearrangements upon infection of primary human endocervical and ectocervical cells. Infect. Immun. 68:53545363.
64. Elkins, C.,, N. H. Carbonetti,, V. A. Varela,, D. Stirewait,, D. G. Klapper, and, P. F. Sparling. 1992. Antibodies to N-terminal peptides of gonococcal porin are bactericidal when gonococcal lipopolysaccharide is not sialylated. Mol. Microbiol. 6:26172628.
65. Evans, B. A. 1977. Ultrastructure study of cervical gonorrhea. J. Infect. Dis. 136:248255.
66. Farzadegan, H., and, I. L. Roth. 1975. Scanning electron microscopy and freeze-etching of gonorrhoeal urethral exudate. Br. J. Vener. Dis. 51:8391.
67. Fichorova, R. N.,, P. J. Desai,, F. C. Gibson III, and, C. A. Genco. 2001. Distinct proinflammatory host responses to Neisseria gonorrhoeae infection in immortalized human cervical and vaginal epithelial cells. Infect. Immun. 69:58405848.
68. Folster, J. P., and, W. M. Shafer. 2005. Regulation of mtrF expression in Neisseria gonorrhoeae and its role in high-level antimicrobial resistance. J. Bacteriol. 187:37133720.
69. Forest, K. T., and, J. A. Tainer. 1997. Type-4 pilus structure: outside to inside and top to bottom—a minireview. Gene 192:165169.
70. Gadzar, A. F.,, V. Kurvari,, A. Virmani,, L. Gollahon,, M. Sakaguchi,, M. Westerfield,, D. Kodagoda,, V. Stasny,, H. T. Cunningham,, I. I. Wistuba,, G. Tomlinson,, V. Tonk,, R. Ashfaq,, A. M. Leitch,, J. D. Minna, and, J. W. Shay. 1998. Characterization of paired tumor and non-tumor cell lines established from patients with breast cancer. Int. J. Cancer 78:766774.
71. Gerbase, A. C.,, J. T. Rowley, and, T. E. Mertens. 1998. Global epidemiology of sexually transmitted diseases. Lancet 351(Suppl. 3):24.
72. Giardina, P. C.,, R. Williams,, D. Lubaroff, and, M. A. Apicella. 1998. Neisseria gonorrhoeae induces focal polymerization of actin in primary human urethral epithelium. Infect. Immun. 66:34163419.
73. Gill, D. B.,, M. Koomey,, J. G. Cannon, and, J. P. Atkinson. 2003. Down-regulation of CD46 by piliated Neisseria gonorrhoeae. J. Exp. Med. 198:13131322.
74. Gómez-Duarte, O. G.,, M. Dehio,, C. A. Guzmán,, G. S. Chhatwal,, C. Dehio, and, T. F. Meyer. 1997. Binding of vitronectin to Opa-expressing Neisseria gonorrhoeae mediates invasion of HeLa cells. Infect. Immun. 65:38573866.
75. Gorby, G. L.,, A. F. Ehrhardt,, M. A. Apicella, and, C. Elkins. 2001. Invasion of human fallopian tube epithelium by Escherichia coli expressing combinations of a gonococcal porin, opacity-associated protein, and chimeric lipo-oligosaccharide. J. Infect. Dis. 184:460472.
76. Grassmé, H.,, E. Gulbins,, B. Brenner,, K. Ferlinz,, K. Sandhoff,, K. Harzer,, F. Lang, and, T. F. Meyer. 1997. Acidic sphingomyelinase mediates entry of Neisseria gonorrhoeae into non-phagocytic cells. Cell 91:605615.
77. Griffiss, J. M.,, J. P. O’Brien,, R. Yamasaki,, G. D. Williams,, P. A. Rice, and, H. Schneider. 1987. Physical heterogeneity of neisserial lipooligosaccharides reflects oligosaccharides that differ in apparent molecular weight, chemical composition, and antigenic expression. Infect. Immun. 55:17921800.
78. Hagen, T. A., and, C. N. Cornelissen. 13 October 2006, posting date. Neisseria gonorrhoeae requires expression of TonB and the putative transporter TdfF to replicate within cervical epithelial cells. Mol. Microbiol. doi:10.1111/j.1365–2958.2006.05429.
79. Haines, K. A.,, J. Reibman,, X. Tang,, M. S. Blake, and, G. Weissmann. 1991. Effects of protein I of Neisseria gonorrhoeae on neutrophil activation: generation of diacylglycerol from phosphatidylcholine via a specific phospholipase C is associated with exocytosis. J. Cell Biol. 114:433442.
80. Haines, K. A.,, L. Yeh,, M. S. Blake,, P. Cristello,, H. Korchak, and, G. Weissmann. 1988. Protein I, a translocatable ion channel from Neisseria gonorrhoeae, selectively inhibits exocytosis from human neutrophils without inhibiting O2 generation. J. Biol. Chem. 263:945951.
81. Handsfield, H. H. 1990. Neisseria gonorrhoeae, p. 16131631. In G. L. Mandell,, R. G. Douglas, Jr., and, J. E. Bennett (ed.), Principles and Practice of Infectious Disease, 3rd ed. Churchill Livingstone, New York, NY.
82. Handsfield, H. H.,, T. O. Lipman,, J. P. Harnisch,, E. Tronca, and, K. K. Holmes. 1974. Asymptomatic gonorrhea in men. Diagnosis, natural course, prevalence and significance. N. Engl. J. Med. 290:117123.
83. Harkness, A. H. 1948. The pathology of gonorrhea. Br. J. Vener. Dis. 24:137147.
84. Harvey, H. A.,, M. P. Jennings,, C. A. Campbell,, R. Williams, and, M. A. Apicella. 2001. Receptor-mediated endocytosis of Neisseria gonorrhoeae into primary human urethral epithelial cells: the role of the asialoglycoprotein receptor. Mol. Microbiol. 42:659672.
85. Harvey, H. A.,, M. R. Ketterer,, A. Preston,, D. Lubaroff,, R. Williams, and, M. A. Apicella. 1997. Ultrastructure analysis of primary human urethral epithelial cell cultures infected with Neisseria gonorrhoeae. Infect. Immun. 65:24202427.
86. Harvey, H. A.,, N. Porat,, C. A. Campbell,, M. P. Jennings,, B. W. Gibson,, N. J. Phillips,, M. A. Apicella, and, M. S. Blake. 2000. Gonococcal lipooligosaccharide is a ligand for the asialoglycoprotein receptor on human sperm. Mol. Microbiol. 36:10591070.
87. Harvey, H. A.,, D. M. B. Post, and, M. A. Apicella. 2002. Immortalization of human urethral epithelial cells: a model for the study of the pathogenesis of and the inflammatory cytokine response to Neisseria gonorrhoeae infection. Infect. Immun. 70:58085815.
88. Harvey, H. A.,, W. E. Swords, and, M. A. Apicella. 2001. The mimicry of human glycolipids and glycosphingolipids in the lipooligosaccharides of pathogenic Neisseria and Haemophilus. J. Autoimmun. 65:24202427.
89. Hasty, L. A.,, J. D. Lambris,, B. A. Lessey,, K. Pruksananoda, and, C. R. Lyttle. 1994. Hormonal regulation of the complement components and receptors throughout the menstrual cycle. Am. J. Obstet. Gynecol. 170:168175.
90. Hauck, C. R., and, T. F. Meyer. 1997. The lysosomal/phagosomal membrane protein h-lamp-1 is a target of the IgA1 protease of Neisseria gonorrhoeae. FEBS Lett. 405:8690.
91. Hauck, C. R., and, T. F. Meyer. 2003. “Small” talk: Opa proteins as mediators of Neisseria-host-cell communication. Curr. Opin. Microbiol. 6:4349.
92. Hedges, S. R.,, M. S. Mayo,, L. Kallman,, J. Mestecky,, E. W. Hook III, and, M. W. Russell. 1999. Limited local and systemic antibody responses to Neisseria gonorrhoeae during uncomplicated genital infections. Infect. Immun. 67:39373946.
93. Hegge, F. T.,, P. G. Hitchen,, F. E. Aas,, H. Kristiansen,, C. Lovold,, W. Egge-Jacobsen,, M. Panico,, W. Y. Leong,, V. Bull,, M. Virji,, H. R. Morris,, A. Dell, and, M. Koomey. 2004. Unique modifications with phosphocholine and phosphoethanolamine define alternate antigenic forms of Neisseria gonorrhoeae type IV pili. Proc. Natl. Acad. Sci. USA 101:1079810803.
94. Hoehn, G.,, T. Gerard, and, V. L. Clark. 1990. Distribution of a protein antigenically related to the major anaerobically induced gonococcal outer membrane protein among Neisseria species. Infect. Immun. 58:39293933.
95. Hook, E. W., III, and, H. H. Handsfield. 1999. Gonococcal infections in the adult, p. 451466. In K. K. Holmes,, P.-A. Mårdh,, P. F. Sparling,, S. M. Lemon,, W. E. Stamm,, P. Piot, and, J. N. Wasserheit (ed.), Sexually Transmitted Diseases, 3rd ed. McGraw-Hill, New York, NY.
96. Householder, T. C.,, W. A. Belli,, S. Lissenden,, J. A. Cole, and, V. L. Clark. 1999. cis- and trans- acting elements involved in regulation of aniA, the gene encoding the major anaerobically induced outer membrane protein in Neisseria gonorrhoeae. J. Bacteriol. 181:541551.
97. Hussain, L. A.,, C. G. Kelly,, A. Rodin,, M. Jourdan, and, T. Lehner. 1995. Investigation of the complement receptor 3 (CD11b/CD18) in human rectal epithelium. Clin. Immunol. Exp. 102:384388.
98. Iglesias, M.,, G. D. Plowman, and, C. D. Woodworth. 1995. Interleukin-6 and inter-leukin-6 soluble receptor regulate proliferation of normal, human papillomavirus-immortalized, and carcinoma-derived cervical cells in vitro. Am. J. Pathol. 146:944952.
99. James, J. F., and, J. Swanson. 1978. Studies on gonococcal infection. XIII. Occurrence of color/opacity colonial variants in clinical cultures. Infect. Immun. 19:332340.
100. Jarvis, G. A. 1994. Analysis of C3 deposition and degradation on Neisseria meningitidis and Neisseria gonorrhoeae. Infect. Immun. 62:17551760.
101. Jarvis, G. A. 1995. Recognition and control of neisserial infection by antibody and complement. Trends Microbiol. 3:198201.
102. Jerse, A. E.,, M. S. Cohen,, P. M. Drown,, L. G. Whicker,, S. F. Isbey,, H. S. Seifert, and, J. G. Cannon. 1994. Multiple gonococcal opacity proteins are expressed during experimental urethral infection in the male. J. Exp. Med. 179:911920.
103. Jerse, A. E.,, N. D. Sharma,, A. N. Simms,, E. T. Crow,, L. A. Synder, and, W. M. Shafer. 2003. A gonococcal efflux pump enhances bacterial survival in a female mouse model of genital tract infection. Infect. Immun. 71:55765582.
104. Johannsen, D. B.,, D. M. Johnston,, H. O. Koymen,, M. S. Cohen, and, J. G. Cannon. 1999. A Neisseria gonorrhoeae immunoglobulin A1 protease mutant is infectious in the human challenge model of urethral infection. Infect. Immun. 67:30093013.
105. John, C. M.,, H. Schneider, and, J. M. Griffiss. 1999. Neisseria gonorrhoeae that infect men have lipooligosaccharides with terminal N-acetyllactosamine repeats. J. Biol. Chem. 274:10171025.
106. Johnson, A. P.,, J. B. Clark,, M. F. Osborn, and, D. Taylor-Robinson. 1980. A comparison of the association of Neisseria gonorrhoeae with human and guinea-pig genital mucosa maintained in organ culture. Br. J. Exp. Pathol. 61:521527.
107. Joiner, K. A.,, R. Scales,, K. A. Warren,, M. M. Frank, and, P. A. Rice. 1985. Mechanism of action of blocking immunoglobulin G for Neisseria gonorrhoeae. J. Clin. Investig. 76:17651772.
108. Källström, H.,, M. K. Liszewski,, J. P. Atkinson, and, A.-B. Jonsson. 1997. Membrane cofactor protein (MCP or CD46) is a cellular pilus receptor for pathogenic Neisseria. Mol. Microbiol. 25:639647.
109. Kaur, P., and, J. K. McDougall. 1988. Characterization of primary human keratinocytes transformed by human papillomavirus type 18. J. Virol. 62:19171924.
110. Killian, M.,, J. Reinholdt,, H. Lomholt,, K. Poulsen, and, E. V. G. Frandsen. 1996. Biological significance of IgA1 proteases in bacterial colonization and pathogenesis: critical evaluation of experimental evidence. APMIS 104:321338.
111. Kim, J. J.,, D. Zhou,, R. E. Mandrell, and, J. M. Griffiss. 1992. Effect of exogenous sialylation of Neisseria gonorrhoeae on opsonophagocytosis. Infect. Immun. 60:44394442.
112. Kirchner, M.,, D. Heuer, and, T. F. Meyer. 2005. CD46-independent binding of neisserial type IV pili and the major pilus adhesin, PilC, to human epithelial cells. Infect. Immun. 73:30723082.
113. Knapp, J. S., and, R. J. Rice. 1996. Neisseria and Branhamella, p. 324340. In P. R. Murray,, E. J. Baron,, M. A. Pfaller,, F. C. Tenover, and, R. H. Yolken (ed.), Manual of Clinical Microbiology, 6th ed. ASM Press, Washington, DC.
114. Kondo, T.,, K. Mihara,, Y. Inoue, and, M. Namba. 1996. Two-dimensional electrophoretic studies on down-regulated intracellular transferrin in human fibroblasts immortalized by treatment with either 4-nitroquinoline 1-oxide or 60Co gamma rays. Electrophoresis 17:16381642.
115. Kraus, D.,, M. E. Medof, and, C. Mold. 1998. Complementary recognition of alternative pathway activators by decay-accelerating factor and factor H. Infect. Immun. 66:399405.
116. Krepler, R.,, H. Denk,, U. Artlieb, and, R. Moll. 1982. Immunocytochemistry of intermediate filament proteins present in pleomorphic adenomas of the human parotid gland: characterization of different cell types in the same tumor. Differentiation 21:191199.
117. Kuhlewein, C.,, C. Rechner,, T. F. Meyer, and, T. Rudel. 2006. Low-phosphate-dependent invasion resembles a general way for Neisseria gonorrhoeae to enter host cells. Infect. Immun. 74:42664273.
118. Lee, S. W.,, D. L. Higashi,, A. Snyder,, A. J. Merz,, L. Potter, and, M. So. 2005. PilT is required for PI(3,4,5)P3-mediated crosstalk between Neisseria gonorrhoeae and epithelial cells. Cell. Microbiol. 7:12711284.
119. Lei, Z. M.,, E. Reshef, and, V. Rao. 1992. The expression of human chorionic gonadotropin/luteinizing hormone receptors in human endometrial and myometrial blood vessels. J. Clin. Endocrinol. Metab. 75:651659.
120. Lei, Z. M.,, P. Toth,, C. V. Rao, and, D. Pridham. 1993. Novel coexpression of human chorionic gonadotropin (hCG)/human luteinizing hormone receptors and their ligand hCG in human fallopian tubes. J. Clin. Endocrinol. Metab. 77:863872.
121. Lemon, S. M., and, P. F. Sparling. 1999. Pathogenesis of sexually transmitted viral and bacterial infections, p. 433449. In K. K. Holmes,, P.-A. Mardh,, P. F. Sparling,, S. M. Lemon,, W. E. Stamm,, P. Piot, and, J. N. Wasserheit (ed.), Sexually Transmitted Diseases, 3rd ed. McGraw-Hill, New York, NY.
122. Lin, J.,, Z. M. Lei,, S. Lojun,, C. V. Rao,, P. G. Satyaswaroop, and, T. G. Day. 1994. Increased expression of luteinizing hormone/human chorionic gonadotropin receptor gene in human endometrial carcinomas. J. Clin. Endocrinol. Metab. 79:14831491.
123. Lin, L.,, P. Ayala,, J. Larson,, M. Mulks,, M. Fukuda,, S. R. Carlsson,, C. Enns, and, M. So. 1997. The Neisseria type 2 IgA1 protease cleaves LAMP1 and promotes survival of bacteria within epithelial cells. Mol. Microbiol. 24:10831094.
124. Lissenden, S.,, S. Mohan,, T. Overton,, T. Regan,, H. Crooke,, J. A. Cardinale,, T. C. Householder,, P. Adams,, C. D. O’Conner,, V. L. Clark,, H. Smith, and, J. A. Cole. 2000. Identification of transcription activators that regulate gonococcal adaptation from aerobic to anaerobic or oxygen-limited growth. Mol. Microbiol. 37:839855.
125. Lorenzen, D. R.,, D. Gunther,, J. Pandit,, T. Rudel,, E. Brandt, and, T. F. Meyer. 2000. Neisseria gonorrhoeae porin modifies the oxidative burst of human professional phagocytes. Infect. Immun. 68:62156222.
126. Maitra, A.,, I. I. Wistuba,, A. K. Virmani,, M. Sakaguchi,, I. Park,, A. Stucky,, S. Milchgrub,, D. Gibbons,, J. D. Minna, and, A. F. Gazdar. 1999. Enrichment of epithelial cells for molecular studies. Nat. Med. 5:459463.
127. Maitra, A.,, I. I. Wistuba,, D. Gibbons,, A. F. Gazdar, and, J. Albores-Saavedra. 1999. Allelic losses at chromosome 3p are seen in human papilloma virus 16 associated transitional cell carcinoma of the cervix. Gynecol. Oncol. 74:361368.
128. Mandrell, R. E. 1992. Further antigenic similarities of Neisseria gonorrhoeae lipooligosaccharides and human glycosphingolipids. Infect. Immun. 60:30173020.
129. Mandrell, R. E., and, M. A. Apicella. 1993. Lipo-oligosaccharides (LOS) of mucosal pathogens: molecular mimicry and host-modification of LOS. Immunobiology 187:382402.
130. Mandrell, R. E.,, J. M. Griffiss, and, B. A. Machers. 1988. Lipooligosaccharides (LOS) of Neisseria gonorrhoeae and Neisseria meningitidis have components that are immunochemically similar to precursors of human blood group antigens. J. Exp. Med. 168:107126.
131. Mandrell, R. E.,, A. J. Lesse,, J. V. Sugai,, J. M. Griffiss,, J. A. Cole,, N. J. Parsons,, H. Smith,, S. A. Morse, and, M. A. Apicella. 1990. In vitro and in vivo modification of Neisseria gonorrhoeae lipopolysaccharide epitope structure by sialylation. J. Exp. Med. 171:16491664.
132. Massari, P.,, Y. Ho, and, L. M. Wetzler. 2003. Neisseria meningitidis porin PorB interacts with mitochondria and protects cells from apoptosis. Proc. Natl. Acad. Sci. USA 97:90709075.
133. McCutchan, J. A.,, D. Katzenstein,, D. Norquist,, G. Chikami,, A. Wunderlich, and, A. I. Braude. 1978. Role of blocking antibody in disseminated gonococcal infection. J. Immunol. 121:18841888.
134. McQuillen, D. P.,, S. Gulati,, S. Ram,, A. K. Turner,, D. B. Jani,, T. C. Heeren, and, P. A. Rice. 1999. Complement processing and immunoglobulin binding to Neisseria gonorrhoeae determined in vitro simulates in vivo effects. J. Infect. Dis. 179:124135.
135. Merz, A. J., and, M. So. 2000. Interactions of pathogenic neisseriae with epithelial cell membranes. Annu. Rev. Cell Dev. Biol. 16:423457.
136. Mickelsen, P. A.,, E. Blackman, and, P. F. Sparling. 1982. Ability of Neisseria gonorrhoeae, Neisseria meningitidis, and commensal Neisseria species to obtain iron from lactoferrin. Infect. Immun. 35:915920.
137. Moll, R.,, W. W. Franke, and, D. L. Schiller. 1982. The catalog of human cytokeratins: patterns of expression in normal epithelia, tumors and cultured cells. Cell 31:1124.
138. Moll, R.,, D. B. von Bassewitz,, U. Schulz, and, W. W. Franke. 1982. An unusual type of cytokeratin filament in cells of a human cloacogenic carcinoma derived from the anorectal transition zone. Differentiation 22:2540.
139. Moran, A. P.,, M. M. Prendergast, and, B. J. Appelmelk. 1996. Molecular mimicry of host structures by bacterial lipopolysaccharides and its contribution to disease. FEMS Immunol. Med. Microbiol. 16:105115.
140. Morse, S. A., and, G. F. Brooks. 1985. Neisseria gonorrhoeae taxonomy, colony phenotypes and disease, p. 38. In G. F. Brooks and, E. A. Donegan (ed.), Gonococcal Infection. Butler and Tanner, Ltd., London, United Kingdom.
141. Mosleh, I. M.,, L. A. Huber,, P. Steinlein,, C. Pasquali,, D. Günther, and, T. F. Meyer. 1998. Neisseria gonorrhoeae porin modulates phagosome maturation. J. Biol. Chem. 273:3533235338.
142. Müller, A.,, D. Gunther,, V. Brinkmann,, R. Hurwitz,, T. F. Meyer, and, T. Rudel. 2000. Targeting of the pro-apoptotic VDAC-like porin (PorB) of Neisseria gonorrhoeae to mitochondria of infected cells. EMBO J. 19:53325343.
143. Müller, A.,, D. Günther,, F. Düx,, M. Naumann,, T. F. Meyer, and, T. Rudel. 1999. Neisserial porin (PorB) causes rapid calcium influx in target cells and induces apoptosis by the activation of cysteine proteases. EMBO J. 18:339352.
144. Naids, F. L., and, R. F. Rest. 1991. Stimulation of human neutrophil oxidative metabolism by nonopsonized Neisseria gonorrhoeae. Infect. Immun. 59:43834390.
145. Novotny, P.,, J. A. Short, and, P. D. Walker. 1975. An electron-microscope study of naturally occurring and cultured cells of Neisseria gonorrhoeae. J. Med. Microbiol. 8:413427.
146. Oglesby, T. J. 1998. The complement system in reproduction, p. 355373. In J. E. Volanakis and, M. M. Frank (ed.), The Human Complement System in Health and Disease. Marcel Dekker, Inc., New York, NY.
147. Overton, T. W.,, R. Whitehead,, Y. Li,, L. A. S. Snyder,, N. J. Saunders,, H. Smith, and, J. A. Cole. 2006. Coordinated regulation of the Neisseria gonorrhoeae truncated denitrification pathway by the nitric oxide-sensitive repressor, NsrR, and the nitirite-insensitive NarQ-NarP. J. Biol. Chem. 281:3311533126.
148. Pantelic, M.,, Y.-J. Kim,, S. Bolland,, I. Chen,, J. Shively, and, T. Chen. 2005. Neisseria gonorrhoeae kills carcinoembryonic antigen-related cellular adhesion molecule 1 (CD66a)-expressing human B cells and inhibits antibody production. Infect. Immun. 73:41714179.
149. Parsons, N. J.,, A. Curry,, A. J. Fox,, D. M. Jones,, J. A. Cole, and, H. Smith. 1992. The serum resistance of gonococci in the majority of urethral exudates is due to sialylated lipopolysaccharide seen as a surface coat. FEMS Microbiol. Lett. 69:295299.
150. Parsons, N. J.,, P. V. Patel,, E. L. Tan,, J. R. C. Andrade,, C. A. Nairn,, M. Goldner,, J. A. Cole, and, H. Smith. 1988. Cytidine 5′-monophospho-N-acetyl neuraminic acid and a low molecular weight factor from human blood cells induce lipopolysaccharide alteration in gonococci when conferring resistance to killing by human serum. Microb. Pathog. 5:303309.
151. Patel, P.,, C. F. Marrs,, J. S. Mattick,, W. W. Ruehl,, R. K. Taylor, and, M. Koomey. 1991. Shared antigenicity and immunogenicity of type 4 pilins expressed by Pseudomonas aeruginosa, Moraxella bovis, Neisseria gonorrhoeae, Dichelobacter nodosus, and Vibrio cholerae. Infect. Immun. 59:46744676.
152. Paulesu, L., and, G. P. Pessina. 1982. Cyclic changes of sialidase in human cervical mucus. Int. J. Biochem. 14:561563.
153. Pellegrino, M. B.,, B. B. Asch,, J. L. Connolly, and, H. L. Asch. 1988. Differential expression of keratins 13 and 16 in normal epithelium, benign lesions, and ductal carcinomas of the human breast determined by the monoclonal antibody Ks8.12. Cancer Res. 48:58315836.
154. Popp, A.,, C. Dehio,, F. Grunert,, T. F. Meyer, and, S. D. Gray-Owen. 1999. Molecular analysis of neisserial Opa protein interactions with the CEA family of receptors: identification of determinants contributing to the differential specificities of binding. Cell. Microbiol. 1:169181.
155. Porat, N.,, M. A. Apicella, and, M. S. Blake. 1995. A lipooligosaccharide-binding site on HepG2 cells similar to the gonococcal opacity-associated surface protein Opa. Infect. Immun. 63:21642172.
156. Post, D. M. B.,, N. J. Phillips,, J. Q. Shao,, D. D. Entz,, B. W. Gibson, and, M. A. Apicella. 2002. Intracellular survival of Neisseria gonorrhoeae in male urethral epithelial cells: importance of a hexaacyl lipid A. Infect. Immun. 70:909920.
157. Preston, A.,, R. E. Mandrell,, B. W. Gibson, and, M. A. Apicella. 1996. The lipooligosaccharides of pathogenic gram-negative bacteria. Crit. Rev. Microbiol. 22:139180.
158. Price, R. J., and, B. Boettcher. 1979. The presence of complement in human cervical mucus and its possible relevance to infertility in women with complement-dependent sperm-immobilizing antibodies. Fertil. Steril. 32:6166.
159. Ram, S.,, D. P. McQuillen,, S. Gulati,, C. Elkins,, M. K. Pangburn, and, P. A. Rice. 1998. Binding of complement factor H to loop 5 of porin protein 1A: a molecular mechanism of serum resistance of nonsialylated Neisseria gonorrhoeae. J. Exp. Med. 188:671680.
160. Ram, S.,, F. G. Mackinnon,, S. Gulati,, D. P. McQuillen,, U. Vogel,, M. Frosch,, C. Elkins,, H.-K. Guttormsen,, L. M. Wetzler,, M. Oppermann,, M. K. Pangburn, and, P. A. Rice. 1999. The contrasting mechanisms of serum resistance of Neisseria gonorrhoeae and group B Neisseria meningitidis. Mol. Immunol. 36:915928.
161. Ram, S.,, A. K. Sharma,, S. D. Simpson,, S. Gulati,, D. P. McQuillen,, M. K. Pangburn, and, P. A. Rice. 1998. A novel sialic acid binding site on factor H mediates serum resistance of sialylated Neisseria gonorrhoeae. J. Exp. Med. 187:743752.
162. Ram, S.,, M. Cullinane,, A. M. Blom,, S. Gulati,, D. P. McQuillen,, B. G. Monks,, C. O’Connell,, R. Boden,, C. Elkins,, M. K. Pangburn,, B. Dahlback, and, P. A. Rice. 2001. Binding of C4b-binding protein to porin: a molecular mechanism of serum resistance of Neisseria gonorrhoeae. J. Exp. Med. 193:281295.
163. Ramsey, K. H.,, H. Schneider,, A. S. Cross,, J. W. Boslego,, D. L. Hoover,, T. L. Staley,, R. A. Kuschner, and, C. D. Deal. 1995. Inflammatory cytokines produced in response to experimental human gonorrhea. J. Infect. Dis. 172:186191.
164. Reinholdt, J., and, M. Killian. 1997. Comparative analysis of immunoglobulin A1 protease activity among bacteria representing different genera, species, and strains. Infect. Immun. 65:44524459.
165. Reshef, E.,, Z. M. Lei,, C. V. Rao,, D. D. Pridham,, N. Chegini, and, J. L. Luborsky. 1990. The presence of gonadotropin receptors in nonpregnant human uterus, human placenta, fetal membranes, and decidua. J. Clin. Endocrinol. Metab. 70:421430.
166. Rest, R. F.,, S. H. Fischer,, Z. Z. Ingham, and, J. F. Jones. 1982. Interactions of Neisseria gonorrhoeae with human neutrophils: effects of serum and gonococcal opacity on phagocyte killing and chemiluminescence. Infect. Immun. 36:737744.
167. Rest, R. F.,, J. Liu,, R. Talukdar,, J. V. Frangipane, and, D. Simon. 1994. Interaction of pathogenic Neisseria with host defenses. What happens in vivo? Ann. N. Y. Acad. Sci. 730:182196.
168. Rice, P. A. 1989. Molecular basis for serum resistance in Neisseria gonorrhoeae. Clin. Microbiol. Rev. 2:S112S117.
169. Rice, P. A., and, D. L. Kasper. 1982. Characterization of serum resistance of Neisseria gonorrhoeae that disseminate. J. Clin. Investig. 70:157167.
170. Rice, P. A.,, H. E. Vayo,, M. R. Tam, and, M. S. Blake. 1986. Immunoglobulin G antibodies directed against protein III block killing of serum-resistant Neisseria gonorrhoeae by immune sera. J. Exp. Med. 164:17351748.
171. Rohde, K. H., and, D. W. Dyer. 2003. Mechanisms of iron acquisition by the human pathogens Neisseria meningitidis and Neisseria gonorrhoeae. Front. Biosci. 8:d1186d1218.
172. Rouquette-Loughlin, C. E.,, J. T. Balthazar, and, W. M. Shafer. 2005. Characterization of the MacA-MacB efflux system in Neisseria gonorrhoeae. J. Antimicrob. Chemother. 56:856860.
173. Rudel, T.,, H.-J. Boxberger, and, T. F. Meyer. 1996. Modulation of Neisseria porin (porB) by cytosolic ATP/GTP of target cells: parallels between pathogen accommodation and mitochondrial endosymbiosis. Cell 85:391402.
174. Schneider, H.,, A. S. Cross,, R. A. Kuschner,, D. N. Taylor,, J. C. Sandoff,, J. W. Boslego, and, C. D. Deal. 1995. Experimental human gonococcal urethritis: 250 Neisseria gonorrhoeae MS11mkC are infective. J. Infect. Dis. 172:180185.
175. Schneider, H.,, J. M. Griffiss,, J. W. Boslego,, P. J. Hitchcock,, K. M. Zahos, and, M. A. Apicella. 1991. Expression of paragloboside-like lipooligosaccharides may be a necessary component of gonococcal pathogenesis in men. J. Exp. Med. 174:16011605.
176. Schneider, H.,, C. A. Hammack,, M. Adanaher,, M. A. Apicella, and, J. M. Griffiss. 1988. Instability of expression of lipooligosaccharides and their epitopes in Neisseria gonorrhoeae. Infect. Immun. 56:942946.
177. Schneider, H.,, K. A. Schmidt,, D. R. Skillman,, L. Van De Verg,, R. L. Warren,, H. J. Wylie,, J. C. Sadoff,, C. D. Deal, and, A. S. Cross. 1996. Sialylation lessens the infectivity of Neisseria gonorrhoeae MS11mkC. J. Infect. Dis. 173:14221427.
178. Schoolnik, G. K.,, R. Fernandez,, J. Y. Tai,, J. Rothbard, and, E. C. Gotschlich. 1984. Gonococcal pili. Primary structure and receptor binding domain. J. Exp. Med. 159:13511370.
179. Schryvers, A. B., and, I. Stojiljkovic. 1999. Iron acquisition systems in the pathogenic Neisseria. Mol. Microbiol. 32:11171123.
180. Seib, K. L.,, H. J. Tseng,, A. G. McEwan,, M. A. Apicella, and, M. P. Jennings. 2004. Defenses against oxidative stress in Neisseria gonorrhoeae and Neisseria meningitidis: distinctive systems for different lifestyles. J. Infect. Dis. 190:136147.
181. Seib, K. L.,, H. J. Wu,, S. P. Kidd,, M. A. Apicella,, M. P. Jennings, and, A. G. McEwan. 2006. Defenses against oxidative stress in Neisseria gonorrhoeae: a system tailored for a challenging environment. Microbiol. Mol. Biol. Rev. 70:344361.
182. Seib, K. L.,, M. P. Simons,, H. J. Wu,, A. G. McEwan,, W. M. Nauseef,, M. A. Apicella, and, M. P. Jennings. 2005. Investigation of oxidative stress defenses of Neisseria gonorrhoeae by using a human polymorphonuclear leukocyte survival assay. Infect. Immun. 73:52695272.
183. Seya, T.,, T. Hara,, M. Matsumoto, and, H. Akedo. 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. 145:238245.
184. Shafer, W. M., and, R. F. Rest. 1989. Interactions of gonococci with phagocytic cells. Annu. Rev. Microbiol. 43:121145.
185. Shaw, J. H.,, F. Hayes,, G. F. Brooks, and, S. Falkow. 1987. Development of a tissue culture model for gonococcal invasion. Antonie Leeuwenhoek 53:485491.
186. Shell, D. M.,, L. Chiles,, R. C. Judd,, S. Seal, and, R. F. Rest. 2002. The Neisseria lipooligosaccharide-specific alpha-2,3-sialyltransferase is a surface-exposed outer membrane protein. Infect. Immun. 70:37443751.
187. Shivapurkar, N.,, S. Sood,, I. I. Wistuba,, A. K. Virmani,, A. Maitra,, S. Milchgrub,, J. D. Minna, and, A. F. Gazdar. 1999. Multiple regions of chromosome 4 demonstrating allelic losses in breast carcinomas. Cancer Res. 59:35763580.
188. Simms, A. N., and, A. E. Jerse. 2006. In vivo selection for Neisseria gonorrhoeae opacity protein expression in the absence of human carcinoembryonic antigen cell adhesion molecules. Infect. Immun. 74:29652974.
189. Simons, M. P.,, W. M. Nauseef, and, M. A. Apicella. 2005. Interactions of Neisseria gonorrhoeae with adherent polymorphonuclear leukocytes. Infect. Immun. 73:19711977.
190. Simons, M. P.,, W. M. Nauseef,, T. S. Griffith, and, M. A. Apicella. 2006. Neisseria gonorrhoeae delays the onset of apoptosis in polymorphonuclear leukocytes. Cell. Microbiol. 8:17801790.
191. Sizemore, N., and, E. A. Rorke. 1993. Human papillomavirus 16 immortalization of normal ectocervical epithelial cells alters retinoic acid regulation of cell growth and epidermal growth factor receptor expression. Cancer Res. 53:45114517.
192. Smedts, F.,, F. Ramaekers,, H. Robben,, M. Pruszczynski,, G. van Muijen,, B. Lane,, I. Leigh, and, P. Vooijs. 1990. Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia. Am. J. Pathol. 136:657668.
193. Smedts, F.,, F. Ramaekers,, S. Troyanovsky,, M. Pruszczynski,, M. Link,, B. Lane,, I. Leigh,, C. Schijf, and, P. Vooijs. 1992. Keratin expression in cervical cancer. Am. J. Pathol. 141:497511.
194. Smith, H.,, N. J. Parsons, and, J. A. Cole. 1995. Sialylation of neisserial lipopolysaccharides: a major influence on pathogenicity. Microb. Pathog. 19:365377.
195. Song, W.,, L. Ma,, R. Chen, and, D. C. Stein. 1991. Role of lipooligosaccharide in Opa-dependent invasion of Neisseria gonorrhoeae into human epithelial cells. J. Exp. Med. 191:949959.
196. Sparling, P. F. 1999. Biology of Neisseria gonorrhoeae, p. 433449. In K. K. Holmes,, P.-A. Mardh,, P. F. Sparling,, S. M. Lemon,, W. E. Stamm,, P. Piot, and, J. N. Wasserheit (ed.), Sexually Transmitted Diseases, 3rd ed. McGraw-Hill, New York, NY.
197. Spence, J. M.,, J. C.-R. Chen, and, V. L. Clark. 1997. A proposed role for the lutropin receptor in contact-inducible gonococcal invasion of Hec1B cells. Infect. Immun. 65:37363742.
198. Spence, J. M.,, R. E. Tyler,, R. A. Domaoal, and, V. L. Clark. 2002. L12 enhances gonococcal transcytosis of polarized Hec1B cells via the lutropin receptor. Microb. Pathog. 32:117125.
199. Stohl, E. A.,, A. K. Criss, and, H. S. Seifert. 2005. The transcriptome response of Neisseria gonorrhoeae to hydrogen peroxide reveals genes with previously uncharacterized roles in oxidative damage protection. Mol. Microbiol. 58:520532.
200. Stone, J. L.,, S. K. Vernon, and, G. H. Warren. 1974. Cultivation and survival studies of Neisseria gonorrhoeae in a human diploid cell strain. Yale J. Biol. Med. 47:291296.
201. Sun, Q.,, K. Tsutsumi,, M. Yokoyama,, M. M. Pater, and, A. Pater. 1993. In vivo cytokeratin-expression pattern of stratified squamous epithelium from human papillomavirus-type-16-immortalized ectocervical and foreskin keratinocytes. Int. J. Cancer 54:656662.
202. Sweet, R. L.,, M. Blankfort-Doyle,, M. O. Robbie, and, J. Schacter. 1986. The occurrence of chlamydial and gonococcal salpingitis during the menstrual cycle. JAMA 255:20622064.
203. Timmerman, M. M.,, J. Q. Shao, and, M. A. Apicella. 2005. Ultrastructure analysis of the pathogenesis of Neisseria gonorrhoeae endometrial infection. Cell. Microbiol. 7:627636.
204. Tobiason, D. M., and, H. S. Seifert. 2001. Inverse relationship between pilus-mediated gonococcal adherence and surface expression of the pilus receptor, CD46. Microbiology 147:23332340.
205. Tramont, E. C. 1989. Gonococcal vaccines. Clin. Microbiol. Rev. 2:S74S77.
206. Turner, S. M.,, J. W. B. Moir,, L. Griffiths,, T. W. Overton,, H. Smith, and, J. A. Cole. 2005. Mutational and biochemical analysis of cytochrome c′, a nitric oxide-binding lipoprotein important for adaptation of Neisseria gonorrhoeae to oxygen-limited growth. Biochem. J. 388:545553.
207. van der Ley, P.,, J. E. Heckels,, M. Virji,, P. Hoogerhout, and, J. T. Poolman. 1991. Topology of outer membrane porins in pathogenic Neisseria spp. Infect. Immun. 59:29632971.
208. Vanderpuye, O. A.,, C. A. Labarrere, and, J. A. McIntyre. 1992. The complement system in reproduction. Fertil. Immunol. 27:145155.
209. van Putten, J. P. 1993. Phase variation of lipopolysaccharide directs interconversion of invasive and immunoresistant phenotypes of Neisseria gonorrhoeae. EMBO J. 12:40434051.
210. van Putten, J. P. M., and, T. D. Duensing. 1997. Infection of mucosal epithelial cells by Neisseria gonorrhoeae. Rev. Med. Microbiol. 8:5159.
211. van Putten, J. P. M.,, T. D. Duensing, and, J. Carlson. 1998. Gonococcal invasion of epithelial cells driven by P.IA, a bacterial ion channel with GTP binding properties. J. Exp. Med. 188:941952.
212. van Putten, J. P. M.,, T. D. Duensing, and, R. L. Cole. 1998. Entry of Opa+ gonococci into Hep-2 cells requires concerted action of glycosaminoglycans, fibronectin and integrin receptors. Mol. Microbiol. 29:369379.
213. van Putten, J. P. M., and, B. D. Robertson. 1995. Molecular mechanisms and implications for infection of lipopolysaccharide variation in Neisseria. Mol. Microbiol. 16:847853.
214. Virji, M.,, S. M. Watt,, S. Barker,, K. Makepeace, and, R. Doyonnas. 1996. The N-domain of the human CD66a adhesion molecule is a target for Opa proteins of Neisseria meningitidis and Neisseria gonorrhoeae. Mol. Microbiol. 22:929939.
215. Virji, M.,, D. Evans,, A. Hadfield,, F. Grunert,, A. M. Teixeira, and, S. M. Watt. 1999. Critical determinants of host receptor targeting by Neisseria meningitidis and Neisseria gonorrhoeae: identification of Opa adhesiotopes on the N-domain of CD66 molecules. Mol. Microbiol. 34:538551.
216. Virji, M., and, J. E. Heckels. 1986. The effect of protein II and pili on the interaction of Neisseria gonorrhoeae with human polymorphonuclear leucocytes. J. Gen. Microbiol. 132:503512.
217. Vogel, U., and, M. Frosch. 1999. Mechanisms of neisserial serum resistance. Mol. Microbiol. 32:11331139.
218. von Bassewitz, D. B.,, A. Roessner, and, E. Grundmann. 1982. Intermediate-sized filaments in cells of normal human colon mucosa, adenomas and carcinomas. Pathol. Res. Pract. 175:238255.
219. Waitkins, S. A., and, J. Flynn. 1973. Intracellular growth and type variation of Neisseria gonorrhoeae in tissue cell-cultures. J. Med. Microbiol. 6:399403.
220. Ward, M. E., and, P. J. Watt. 1972. Adherence of Neisseria gonorrhoeae to urethral mucosal cells: an electron-microscopic study of human gonorrhea. J. Infect. Dis. 126:601605.
221. Weel, J. F. L., and, J. P. M. van Putten. 1991. Fate of the major outer membrane protein P.IA in early and late events of gonococcal infection of epithelial cells. Res. Microbiol. 142:985993.
222. Wen, K.-K.,, P. C. Giardina,, M. S. Blake,, J. L. Edwards,, M. A. Apicella, and, P. A. Rubenstein. 2000. Interaction of the gonococcal porin P.IB with G- and F-actin. Biochemistry 39:86388647.
223. West, S. E., and, P. F. Sparling. 1985. Response of Neisseria gonorrhoeae to iron limitation: alterations in expression of membrane proteins without apparent siderophore production. Infect. Immun. 47:388394.
224. West, S. E., and, P. F. Sparling. 1987. Aerobactin utilization by Neisseria gonorrhoeae and cloning of a genomic DNA fragment that complements Escherichia coli fhuB mutations. J. Bacteriol. 169:34143421.
225. Williams, J. M.,, G.-C. Chen,, L. Zhu, and, R. F. Rest. 1998. Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth. Mol. Microbiol. 27:171186.
226. Workowski, K. A., and, W. C. Levine. 2002. Sexually transmitted diseases treatment guidelines, 2002. Morb. Mortal. Wkly. Rep. 51(RR06):180.
227. Wright, S. D., and, S. C. Silverstein. 1983. Receptors for C3b and C3bi promote phagocytosis but not the release of toxic oxygen from human phagocytes. J. Exp. Med. 158:20162023.
228. Yamamoto, K., and, R. B. Johnston. 1984. Dissociation of phagocytosis from stimulation of the oxidative metabolic burst in macrophages. J. Exp. Med. 159:405416.
229. Yang, Q. L., and, E. C. Gotschlich. 1996. Variation of gonococcal lipooligosaccharide structure is due to alterations in poly-G tracts in lgt genes encoding glycosyl transferases. J. Exp. Med. 183:323327.
230. Young, J. D.-E.,, M. Blake,, A. Mauro, and, Z. A. Cohn. 1983. Properties of the major outer membrane protein from Neisseria gonorrhoeae incorporated into model lipid membranes. Infect. Immun. 68:62156222.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error