Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1982 Oct 1;156(4):1235–1249. doi: 10.1084/jem.156.4.1235

Activation of complement by serum-resistant Neisseria gonorrhoeae. Assembly of the membrane attack complex without subsequent cell death

PMCID: PMC2186825  PMID: 6818318

Abstract

Interaction of the human complement system in normal human serum (NHS) with serum-resistant and -sensitive Neisseria gonorrhoeae was evaluated to better understand the mechanism of serum-resistance. Complement activity (CH50) was depleted from NHS in a dose-dependent fashion by both serum-resistant and -sensitive N. gonorrhoeae. No detectable CH50 remained in NHS incubated with 10(9) colony-forming units (CFU)/ml serum of either resistant or sensitive strains. When smaller numbers of bacteria were incubated with NHS, lesser, yet comparable, amounts of CH50 were depleted by both resistant and sensitive strains. Hemolytic C2 activity was diminished by 33% in the case of resistant N. gonorrhoeae (10(8) CFU/ml serum) and by 48% in the case of a sensitive strain. No detectable decreases in hemolytic C4 or C7 activities were found with either sensitive or resistant strains at this concentration. Both resistant and sensitive strains activated C1s in NHS. Resistant strains specifically activated 19-21% of radiolabeled C1s in NHS, whereas sensitive strains activated 18-32%. Both resistant and sensitive strains also activated C5 in NHS. In binding assays using radiolabeled C5 and C9 in NHS, resistant and sensitive strains bound comparable amounts of C5 and C9. The number of bound C5 and C9 molecules varied according to the number of bacteria or amount of serum used in the assay. The ratio of C9/C5 bound to a sensitive strain was 6.8, and to a resistant strain was 8.2, suggesting that C5 and C9 were incorporated into membrane attack complexes (MAC). Electron microscopic examination of resistant and sensitive strains incubated with NHS revealed that MAC is bound to the surfaces of the resistant strain as well as the sensitive strain.

Full Text

The Full Text of this article is available as a PDF (1.8 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. ADLER F. L. Studies on the bactericidal reaction. II. Inhibition by antibody, and antibody requirements of the reaction. J Immunol. 1953 Jan;70(1):79–88. [PubMed] [Google Scholar]
  2. Bartholomew R. M., Esser A. F. The first complement component: evidence for an equilibrium between C1s free in serum and C1s bound in the C1 complex. J Immunol. 1977 Dec;119(6):1916–1922. [PubMed] [Google Scholar]
  3. Biesecker G., Müller-Eberhard H. J. The ninth component of human complement: purification and physicochemical characterization. J Immunol. 1980 Mar;124(3):1291–1296. [PubMed] [Google Scholar]
  4. Eisenstein B. I., Lee T. J., Sparling P. F. Penicillin sensitivity and serum resistance are independent attributes of strains of Neisseria gonorrhoeae causing disseminated gonococcal infection. Infect Immun. 1977 Mar;15(3):834–841. doi: 10.1128/iai.15.3.834-841.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fraker P. J., Speck J. C., Jr Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun. 1978 Feb 28;80(4):849–857. doi: 10.1016/0006-291x(78)91322-0. [DOI] [PubMed] [Google Scholar]
  6. Griffiss J. M. Bactericidal activity of meningococcal antisera. Blocking by IgA of lytic antibody in human convalescent sera. J Immunol. 1975 Jun;114(6):1779–1784. [PubMed] [Google Scholar]
  7. Guttman R. M., Waisbren B. A. Bacterial blocking activity of specific IgG in chronic Pseudomonas aeruginosa infection. Clin Exp Immunol. 1975 Jan;19(1):121–130. [PMC free article] [PubMed] [Google Scholar]
  8. Hammer C. H., Wirtz G. H., Renfer L., Gresham H. D., Tack B. F. Large scale isolation of functionally active components of the human complement system. J Biol Chem. 1981 Apr 25;256(8):3995–4006. [PubMed] [Google Scholar]
  9. Harriman G. R., Esser A. F., Podack E. R., Wunderlich A. C., Braude A. I., Lint T. F., Curd J. G. The role of C9 in complement-mediated killing of Neisseria. J Immunol. 1981 Dec;127(6):2386–2390. [PubMed] [Google Scholar]
  10. Joiner K. A., Hammer C. H., Brown E. J., Cole R. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. I. Terminal complement components are deposited and released from Salmonella minnesota S218 without causing bacterial death. J Exp Med. 1982 Mar 1;155(3):797–808. doi: 10.1084/jem.155.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Joiner K. A., Hammer C. H., Brown E. J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. II. C8 and C9 release C5b67 from the surface of Salmonella minnesota S218 because the terminal complex does not insert into the bacterial outer membrane. J Exp Med. 1982 Mar 1;155(3):809–819. doi: 10.1084/jem.155.3.809. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. KELLOGG D. S., Jr, PEACOCK W. L., Jr, DEACON W. E., BROWN L., PIRKLE D. I. NEISSERIA GONORRHOEAE. I. VIRULENCE GENETICALLY LINKED TO CLONAL VARIATION. J Bacteriol. 1963 Jun;85:1274–1279. doi: 10.1128/jb.85.6.1274-1279.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kolb W. P., Müller-Eberhard H. J. The membrane attack mechanism of complement. Verification of a stable C5-9 complex in free solution. J Exp Med. 1973 Aug 1;138(2):438–451. doi: 10.1084/jem.138.2.438. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  15. McCutchan J. A., Katzenstein D., Norquist D., Chikami G., Wunderlich A., Braude A. I. Role of blocking antibody in disseminated gonococcal infection. J Immunol. 1978 Nov;121(5):1884–1888. [PubMed] [Google Scholar]
  16. McCutchan J. A., Levine S., Braude A. I. Influence of colony type on susceptibility of gonococci to killing by human serum. J Immunol. 1976 Jun;116(6):1652–1655. [PubMed] [Google Scholar]
  17. Podack E. R., Kolb W. P., Esser A. F., Müller-Eberhard H. J. Structural similarities between C6 and C7 of human complement. J Immunol. 1979 Sep;123(3):1071–1077. [PubMed] [Google Scholar]
  18. Rice P. A., Goldenberg D. L. Clinical manifestations of disseminated infection caused by Neisseria gonorrhoeae are linked to differences in bactericidal reactivity of infecting strains. Ann Intern Med. 1981 Aug;95(2):175–178. doi: 10.7326/0003-4819-95-2-175. [DOI] [PubMed] [Google Scholar]
  19. Rice P. A., McCormack W. M., Kasper D. L. Natural serum bactericidal activity against Neisseria gonorrhoeae isolates from disseminated, locally invasive, and uncomplicated disease. J Immunol. 1980 May;124(5):2105–2109. [PubMed] [Google Scholar]
  20. Schoolnik G. K., Buchanan T. M., Holmes K. K. Gonococci causing disseminated gonococcal infection are resistant to the bactericidal action of normal human sera. J Clin Invest. 1976 Nov;58(5):1163–1173. doi: 10.1172/JCI108569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Spink W. W., Keefer C. S. STUDIES OF GONOCOCCAL INFECTION. II. THE BACTERIOLYTIC POWER OF THE WHOLE DEFIBRINATED BLOOD OF PATIENTS WITH GONOCOCCAL ARTHRITIS. J Clin Invest. 1937 Mar;16(2):177–183. doi: 10.1172/JCI100845. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Swanson J., Goldschneider I. The serum bactericidal system: ultrastructural changes in Neisseria meningitidis exposed to normal rat serum. J Exp Med. 1969 Jan 1;129(1):51–79. doi: 10.1084/jem.129.1.51. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Swanson J., Kraus S. J., Gotschlich E. C. Studies on gonococcus infection. I. Pili and zones of adhesion: their relation to gonococcal growth patterns. J Exp Med. 1971 Oct 1;134(4):886–906. doi: 10.1084/jem.134.4.886. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Ward M. E., Watt P. J., Glynn A. A. Gonococci in urethral exudates possess a virulence factor lost on subculture. Nature. 1970 Jul 25;227(5256):382–384. doi: 10.1038/227382a0. [DOI] [PubMed] [Google Scholar]
  25. Wright S. D., Levine R. P. How complement kills E. coli. I. Location of the lethal lesion. J Immunol. 1981 Sep;127(3):1146–1151. [PubMed] [Google Scholar]
  26. Wright S. D., Levine R. P. How complement kills E. coli. II. The apparent two-hit nature of the lethal event. J Immunol. 1981 Sep;127(3):1152–1156. [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES