Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1988 May;81(5):1434–1444. doi: 10.1172/JCI113474

Pathogenesis of Campylobacter fetus infections. Failure of encapsulated Campylobacter fetus to bind C3b explains serum and phagocytosis resistance.

M J Blaser 1, P F Smith 1, J E Repine 1, K A Joiner 1
PMCID: PMC442575  PMID: 3366901

Abstract

Campylobacter fetus ssp. fetus strains causing systemic infections in humans are highly resistant to normal and immune serum, which is due to the presence of high molecular weight (100,000, 127,000, or 149,000) surface (S-layer) proteins. Using serum-resistant parental strains (82-40 LP and 23D) containing the 100,000-mol wt protein and serum-sensitive mutants (82-40 HP and 23B) differing only in that they lack the 100,000-mol wt protein capsule, we examined complement binding and activation, and opsono-phagocytosis by polymorphonuclear leukocytes. C3 consumption was similar for all four strains but C3 was not efficiently bound to 82-40 LP or 23D even in the presence of immune serum, and the small amount of C3 bound was predominently the hemolytically inactive iC3b fragment. Consumption and binding of C5 and C9 was significantly greater for the unencapsulated than the encapsulated strains. Opsonization of 82-40 HP with heat-inactivated normal human serum caused greater than 99% killing by human PMN. Similar opsonization of 82-40 LP showed no kill, but use of immune serum restored killing. Findings in a PMN chemiluminescence assay showed parallel results. Association of 32P-labeled 82-40 HP with PMN in the presence of HINHS was 19-fold that for the 82-40 LP, and electron microscopy illustrated that the difference was in uptake rather than in binding. These results indicate that presence of the 100,000-mol wt protein capsule on the surface of C. fetus leads to impaired C3b binding, thus explaining serum resistance and defective opsonization in NHS, mechanisms that explain the capacity of this enteric organism to cause systemic infections.

Full text

PDF
1434

Images in this article

1436Image
on p.1436
1438Image
on p.1438
1442Image
on p.1442
1442Image
on p.1442

Selected References

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

  1. Blaser M. J., Duncan D. J. Human serum antibody response to Campylobacter jejuni infection as measured in an enzyme-linked immunosorbent assay. Infect Immun. 1984 May;44(2):292–298. doi: 10.1128/iai.44.2.292-298.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blaser M. J. Extraintestinal Campylobacter infections. West J Med. 1986 Mar;144(3):353–354. [PMC free article] [PubMed] [Google Scholar]
  3. Blaser M. J., Hopkins J. A., Berka R. M., Vasil M. L., Wang W. L. Identification and characterization of Campylobacter jejuni outer membrane proteins. Infect Immun. 1983 Oct;42(1):276–284. doi: 10.1128/iai.42.1.276-284.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blaser M. J., Hopkins J. A., Perez-Perez G. I., Cody H. J., Newell D. G. Antigenicity of Campylobacter jejuni flagella. Infect Immun. 1986 Jul;53(1):47–52. doi: 10.21236/ada265460. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Blaser M. J., Hopkins J. A., Vasil M. L. Campylobacter jejuni outer membrane proteins are antigenic for humans. Infect Immun. 1984 Mar;43(3):986–993. doi: 10.1128/iai.43.3.986-993.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blaser M. J., Reller L. B. Campylobacter enteritis. N Engl J Med. 1981 Dec 10;305(24):1444–1452. doi: 10.1056/NEJM198112103052404. [DOI] [PubMed] [Google Scholar]
  7. Blaser M. J., Smith P. F., Hopkins J. A., Heinzer I., Bryner J. H., Wang W. L. Pathogenesis of Campylobacter fetus infections: serum resistance associated with high-molecular-weight surface proteins. J Infect Dis. 1987 Apr;155(4):696–706. doi: 10.1093/infdis/155.4.696. [DOI] [PubMed] [Google Scholar]
  8. Blaser M. J., Smith P. F., Kohler P. F. Susceptibility of Campylobacter isolates to the bactericidal activity of human serum. J Infect Dis. 1985 Feb;151(2):227–235. doi: 10.1093/infdis/151.2.227. [DOI] [PubMed] [Google Scholar]
  9. Bokkenheuser V. Vibrio fetus infection in man. I. Ten new cases and some epidemiologic observations. Am J Epidemiol. 1970 Apr;91(4):400–409. doi: 10.1093/oxfordjournals.aje.a121150. [DOI] [PubMed] [Google Scholar]
  10. Brown E. J., Hosea S. W., Hammer C. H., Burch C. G., Frank M. M. A quantitative analysis of the interactions of antipneumococcal antibody and complement in experimental pneumococcal bacteremia. J Clin Invest. 1982 Jan;69(1):85–98. doi: 10.1172/JCI110444. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DeChatelet L. R. Initiation of the respiratory burst in human polymorphonuclear neutrophils: a critical review. J Reticuloendothel Soc. 1978 Jul;24(1):73–91. [PubMed] [Google Scholar]
  12. Gordon D. L., Johnson G. M., Hostetter M. K. Ligand-receptor interactions in the phagocytosis of virulent Streptococcus pneumoniae by polymorphonuclear leukocytes. J Infect Dis. 1986 Oct;154(4):619–626. doi: 10.1093/infdis/154.4.619. [DOI] [PubMed] [Google Scholar]
  13. Grebner J. V., Mills E. L., Gray G. H., Quie P. G. Comparison of phagocytic and chemiluminescence response of human polymorphonuclear neutrophils. J Lab Clin Med. 1977 Jan;89(1):153–159. [PubMed] [Google Scholar]
  14. Guerrant R. L., Lahita R. G., Winn W. C., Jr, Roberts R. B. Campylobacteriosis in man: pathogenic mechanisms and review of 91 bloodstream infections. Am J Med. 1978 Oct;65(4):584–592. doi: 10.1016/0002-9343(78)90845-8. [DOI] [PubMed] [Google Scholar]
  15. Gupta R. C., Laforce F. M., Mills D. M. Polymorphonuclear leukocyte inclusions and impaired bacterial killing in patients with Felty's syndrome. J Lab Clin Med. 1976 Aug;88(2):183–193. [PubMed] [Google Scholar]
  16. 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]
  17. Harriman G. R., Podack E. R., Braude A. I., Corbeil L. C., Esser A. F., Curd J. G. Activation of complement by serum-resistant Neisseria gonorrhoeae. Assembly of the membrane attack complex without subsequent cell death. J Exp Med. 1982 Oct 1;156(4):1235–1249. doi: 10.1084/jem.156.4.1235. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Harrison R. A., Lachmann P. J. The physiological breakdown of the third component of human complement. Mol Immunol. 1980 Jan;17(1):9–20. doi: 10.1016/0161-5890(80)90119-4. [DOI] [PubMed] [Google Scholar]
  19. Horwitz M. A., Silverstein S. C. Influence of the Escherichia coli capsule on complement fixation and on phagocytosis and killing by human phagocytes. J Clin Invest. 1980 Jan;65(1):82–94. doi: 10.1172/JCI109663. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Iwata K., Kanda Y., Yamaguchi H. Electron microscopic study on phagocytosis of staphylococci by mouse peritoneal macrophages. Infect Immun. 1978 Feb;19(2):649–658. doi: 10.1128/iai.19.2.649-658.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Joiner K. A., Goldman R., Schmetz M., Berger M., Hammer C. H., Frank M. M., Leive L. A quantitative analysis of C3 binding to O-antigen capsule, lipopolysaccharide, and outer membrane protein of E. coli 0111B4. J Immunol. 1984 Jan;132(1):369–375. [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Joiner K. A., Warren K. A., Brown E. J., Swanson J., Frank M. M. Studies on the mechanism of bacterial resistance to complement-mediated killing. IV. C5b-9 forms high molecular weight complexes with bacterial outer membrane constituents on serum-resistant but not on serum-sensitive Neisseria gonorrhoeae. J Immunol. 1983 Sep;131(3):1443–1451. [PubMed] [Google Scholar]
  25. Law S. K., Levine R. P. Interaction between the third complement protein and cell surface macromolecules. Proc Natl Acad Sci U S A. 1977 Jul;74(7):2701–2705. doi: 10.1073/pnas.74.7.2701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Lee M. M., Welliver R. C., La Scolea L. J., Jr Campylobacter meningitis in childhood. Pediatr Infect Dis. 1985 Sep-Oct;4(5):544–547. doi: 10.1097/00006454-198509000-00021. [DOI] [PubMed] [Google Scholar]
  27. Lian C. J., Pai C. H. Inhibition of human neutrophil chemiluminescence by plasmid-mediated outer membrane proteins of Yersinia enterocolitica. Infect Immun. 1985 Jul;49(1):145–151. doi: 10.1128/iai.49.1.145-151.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. McCoy E. C., Doyle D., Burda K., Corbeil L. B., Winter A. J. Superficial antigens of Campylobacter (Vibrio) fetus: characterization of antiphagocytic component. Infect Immun. 1975 Mar;11(3):517–525. doi: 10.1128/iai.11.3.517-525.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Müller-Eberhard H. J., Schreiber R. D. Molecular biology and chemistry of the alternative pathway of complement. Adv Immunol. 1980;29:1–53. doi: 10.1016/s0065-2776(08)60042-5. [DOI] [PubMed] [Google Scholar]
  30. Perez-Perez G. I., Blaser M. J., Bryner J. H. Lipopolysaccharide structures of Campylobacter fetus are related to heat-stable serogroups. Infect Immun. 1986 Jan;51(1):209–212. doi: 10.21236/ada265573. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Perez-Perez G. I., Hopkins J. A., Blaser M. J. Lipopolysaccharide structures in Enterobacteriaceae, Pseudomonas aeruginosa, and Vibrio cholerae are immunologically related to Campylobacter spp. Infect Immun. 1986 Jan;51(1):204–208. doi: 10.1128/iai.51.1.204-208.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Repine J. E., Johansen K. S., Berger E. M. Hydroxyl radical scavengers produce similar decreases in the chemiluminescence responses and bactericidal activities of neutrophils. Infect Immun. 1984 Jan;43(1):435–437. doi: 10.1128/iai.43.1.435-437.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Riley L. W., Finch M. J. Results of the first year of national surveillance of Campylobacter infections in the United States. J Infect Dis. 1985 May;151(5):956–959. doi: 10.1093/infdis/151.5.956. [DOI] [PubMed] [Google Scholar]
  34. Smibert R. M. The genus Campylobacter. Annu Rev Microbiol. 1978;32:673–709. doi: 10.1146/annurev.mi.32.100178.003325. [DOI] [PubMed] [Google Scholar]
  35. Tamplin M. L., Specter S., Rodrick G. E., Friedman H. Vibrio vulnificus resists phagocytosis in the absence of serum opsonins. Infect Immun. 1985 Sep;49(3):715–718. doi: 10.1128/iai.49.3.715-718.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Taylor P. W. Bactericidal and bacteriolytic activity of serum against gram-negative bacteria. Microbiol Rev. 1983 Mar;47(1):46–83. doi: 10.1128/mr.47.1.46-83.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Verhoef J., Peterson P. K., Quie P. G. Kinetics of staphylococcal opsonization, attachment, ingestion and killing by human polymorphonuclear leukocytes: a quantitative assay using [3H]thymidine labeled bacteria. J Immunol Methods. 1977;14(3-4):303–311. doi: 10.1016/0022-1759(77)90141-7. [DOI] [PubMed] [Google Scholar]
  38. Winter A. J., McCoy E. C., Fullmer C. S., Burda K., Bier P. J. Microcapsule of Campylobacter fetus: chemical and physical characterization. Infect Immun. 1978 Dec;22(3):963–971. doi: 10.1128/iai.22.3.963-971.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES