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. 1988 Jan;56(1):40–44. doi: 10.1128/iai.56.1.40-44.1988

Lipopolysaccharide phase variation determines the complement-mediated serum susceptibility of Coxiella burnetii.

S Vishwanath 1, T Hackstadt 1
PMCID: PMC259230  PMID: 3335408

Abstract

Phase variation of Coxiella burnetii is due to variation of the lipopolysaccharide (LPS), a phenomenon analogous to smooth-to-rough LPS variation of gram-negative enteric bacteria. Virulent enterobacteria usually have a smooth LPS and resist serum killing, whereas avirulent rough LPS mutants are sensitive to complement-mediated serum killing. Like gram-negative enterobacteria, smooth LPS phase variants of C. burnetii are virulent, whereas the rough LPS variants are avirulent. We therefore studied the effects of human serum on the LPS variants of the Nine Mile strain of C. burnetii. Analogous to gram-negative enterobacteria, the smooth and intermediate LPS C. burnetii phase variants were resistant to complement-mediated serum killing, whereas the rough LPS variants were killed by serum complement. Although the smooth and intermediate LPS variants were serum resistant, they differed in their interactions with the complement system. The smooth LPS variant activated complement poorly and did not bind C3b; however, the intermediate LPS variant activated complement and bound C3b. The rough LPS variant activated complement via the alternative pathway, whereas the intermediate LPS variant activated the classical pathway. These results provide an explanation for the avirulent nature of the rough LPS variant of C. burnetii and suggest that differences in C. burnetii LPS structure influence the interactions of the LPS phase variants with the complement system.

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Selected References

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

  1. Amano K., Williams J. C., Missler S. R., Reinhold V. N. Structure and biological relationships of Coxiella burnetii lipopolysaccharides. J Biol Chem. 1987 Apr 5;262(10):4740–4747. [PubMed] [Google Scholar]
  2. Baca O. G., Paretsky D. Q fever and Coxiella burnetii: a model for host-parasite interactions. Microbiol Rev. 1983 Jun;47(2):127–149. doi: 10.1128/mr.47.2.127-149.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cooper N. R., Morrison D. C. Binding and activation of the first component of human complement by the lipid A region of lipopolysaccharides. J Immunol. 1978 Jun;120(6):1862–1868. [PubMed] [Google Scholar]
  4. Fiset P., Ormsbee R. A., Silberman R., Peacock M., Spielman S. H. A microagglutination technique for detection and measurement of rickettsial antibodies. Acta Virol. 1969 Jan;13(1):60–66. [PubMed] [Google Scholar]
  5. Gee A. P. Molecular titration of components of the classical complement pathway. Methods Enzymol. 1983;93:339–375. doi: 10.1016/s0076-6879(83)93052-5. [DOI] [PubMed] [Google Scholar]
  6. Grossman N., Leive L. Complement activation via the alternative pathway by purified Salmonella lipopolysaccharide is affected by its structure but not its O-antigen length. J Immunol. 1984 Jan;132(1):376–385. [PubMed] [Google Scholar]
  7. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  8. Hackstadt T., Peacock M. G., Hitchcock P. J., Cole R. L. Lipopolysaccharide variation in Coxiella burnetti: intrastrain heterogeneity in structure and antigenicity. Infect Immun. 1985 May;48(2):359–365. doi: 10.1128/iai.48.2.359-365.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Hinrichs D. J., Jerrells T. R. In vitro evaluation of immunity to Coxiella burnetii. J Immunol. 1976 Sep;117(3):996–1003. [PubMed] [Google Scholar]
  10. Humphres R. C., Hinrichs D. J. Role of antibody in Coxiella burnetii infection. Infect Immun. 1981 Feb;31(2):641–645. doi: 10.1128/iai.31.2.641-645.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Joiner K. A., Brown E. J., Frank M. M. Complement and bacteria: chemistry and biology in host defense. Annu Rev Immunol. 1984;2:461–491. doi: 10.1146/annurev.iy.02.040184.002333. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. Joiner K. A., Schmetz M. A., Goldman R. C., Leive L., Frank M. M. Mechanism of bacterial resistance to complement-mediated killing: inserted C5b-9 correlates with killing for Escherichia coli O111B4 varying in O-antigen capsule and O-polysaccharide coverage of lipid A core oligosaccharide. Infect Immun. 1984 Jul;45(1):113–117. doi: 10.1128/iai.45.1.113-117.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Moos A., Hackstadt T. Comparative virulence of intra- and interstrain lipopolysaccharide variants of Coxiella burnetii in the guinea pig model. Infect Immun. 1987 May;55(5):1144–1150. doi: 10.1128/iai.55.5.1144-1150.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Morrison D. C., Kline L. F. Activation of the classical and properdin pathways of complement by bacterial lipopolysaccharides (LPS). J Immunol. 1977 Jan;118(1):362–368. [PubMed] [Google Scholar]
  18. Nelson B., Ruddy S. Enhancing role of IgG in lysis of rabbit erythrocytes by the alternative pathway of human complement. J Immunol. 1979 May;122(5):1994–1999. [PubMed] [Google Scholar]
  19. Pluschke G., Achtman M. Degree of antibody-independent activation of the classical complement pathway by K1 Escherichia coli differs with O antigen type and correlates with virulence of meningitis in newborns. Infect Immun. 1984 Feb;43(2):684–692. doi: 10.1128/iai.43.2.684-692.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Roantree R. J., Rantz L. A. A STUDY OF THE RELATIONSHIP OF THE NORMAL BACTERICIDAL ACTIVITY OF HUMAN SERUM TO BACTERIAL INFECTION. J Clin Invest. 1960 Jan;39(1):72–81. doi: 10.1172/JCI104029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. STOKER M. G., FISET P. Phase variation of the Nine Mile and other strains of Rickettsia burneti. Can J Microbiol. 1956 May;2(3):310–321. doi: 10.1139/m56-036. [DOI] [PubMed] [Google Scholar]
  22. Schramek S., Mayer H. Different sugar compositions of lipopolysaccharides isolated from phase I and pure phase II cells of Coxiella burnetii. Infect Immun. 1982 Oct;38(1):53–57. doi: 10.1128/iai.38.1.53-57.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Schramek S., Radziejewska-Lebrecht J., Mayer H. 3-C-branched aldoses in lipopolysaccharide of phase I Coxiella burnetii and their role as immunodominant factors. Eur J Biochem. 1985 May 2;148(3):455–461. doi: 10.1111/j.1432-1033.1985.tb08861.x. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Taylor P. W., Kroll H. P. Interaction of human complement proteins with serum-sensitive and serum-resistant strains of Escherichia coli. Mol Immunol. 1984 Jul;21(7):609–620. doi: 10.1016/0161-5890(84)90046-4. [DOI] [PubMed] [Google Scholar]
  26. Thjøtta T., Waaler E. Dissociation and Sensitiveness to Normal Serum in Dysentery Bacilli of Type III. J Bacteriol. 1932 Oct;24(4):301–316. doi: 10.1128/jb.24.4.301-316.1932. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Vukajlovich S. W., Hoffman J., Morrison D. C. Activation of human serum complement by bacterial lipopolysaccharides: structural requirements for antibody independent activation of the classical and alternative pathways. Mol Immunol. 1987 Apr;24(4):319–331. doi: 10.1016/0161-5890(87)90173-8. [DOI] [PubMed] [Google Scholar]
  28. Williams J. C., Peacock M. G., McCaul T. F. Immunological and biological characterization of Coxiella burnetii, phases I and II, separated from host components. Infect Immun. 1981 May;32(2):840–851. doi: 10.1128/iai.32.2.840-851.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]

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