Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1979 Mar;23(3):758–763. doi: 10.1128/iai.23.3.758-763.1979

Lipid A and Anti-Lipid A

Inger Mattsby-Baltzer 1, Bertil Kaijser 1
PMCID: PMC414231  PMID: 378836

Abstract

Lipid A in free form, in crude antigen preparations, and on Formalin-treated Escherichia coli and Salmonella minnesota R595 was employed in studies of its antigenic composition, immunogenicity, and availability on gram-negative bacteria. Analyses with immunodiffusion and crossed immunoelectrophoresis of isolated lipid A preparations revealed three components. Inhibition experiments with enzyme-linked immunosorbent assay showed that the lipid A structure was not exposed on the tested smooth or rough E. coli strains or on S. minnesota R595. In crude O antigen preparations from some of the strains, however, lipid A was available for reaction with antibodies. The inaccessibility of lipid A on the bacterial surface may explain the poor protective capacity of anti-lipid A antibodies against bacterial infections. An enzyme-linked immunosorbent assay was more sensitive for measuring anti-lipid A antibody activity than indirect hemolysis or indirect hemagglutination. With an enzyme-linked immunosorbent assay it was shown that in rabbits the immunogenicity of lipid A was approximately the same when coated on erythrocytes or, as is more commonly done, when lipid A-coated hydrolyzed bacteria were used. Some antisera from rabbits immunized with E. coli of different serotypes showed activity against lipid A, with a higher frequency for antisera from rabbits immunized with R mutants.

Full text

PDF
758

Images in this article

Selected References

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

  1. BECKMANN I., LUEDERITZ O., WESTPHAL O. ZUR IMMUNCHEMIE DER SOMATISCHEN ANTIGENE VON ENTEROBACTERIACEAE. IX. SEROLOGISCHE TYPISIERUNG VON SALMONELLA-R-ANTIGENEN. Biochem Z. 1964 May 22;339:401–415. [PubMed] [Google Scholar]
  2. BURTON A. J., CARTER H. E. PURIFICATION AND CHARACTERIZATION OF THE LIPID A COMPONENT OF THE LIPOPOLYSACCHARIDES FROM ESCHERICHIA COLI. Biochemistry. 1964 Mar;3:411–418. doi: 10.1021/bi00891a018. [DOI] [PubMed] [Google Scholar]
  3. Braude A. I., Douglas H. Passive immunization against the local Shwartzman reaction. J Immunol. 1972 Feb;108(2):505–512. [PubMed] [Google Scholar]
  4. Bruins S. C., Stumacher R., Johns M. A., McCabe W. R. Immunization with R mutants of Salmonella minnesota. II. Comparison of the protective effect of immunization with lipid A and the Re mutant. Infect Immun. 1977 Jul;17(1):16–20. doi: 10.1128/iai.17.1.16-20.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Chang C. C., Nowotny Relation of structure to function in bacterial O-antigens--VII. Endotoxicity of 'lipid A'. Immunochemistry. 1975 Jan;12(1):19–28. doi: 10.1016/0019-2791(75)90045-2. [DOI] [PubMed] [Google Scholar]
  6. Engvall E., Perlmann P. Enzyme-linked immunosorbent assay, Elisa. 3. Quantitation of specific antibodies by enzyme-labeled anti-immunoglobulin in antigen-coated tubes. J Immunol. 1972 Jul;109(1):129–135. [PubMed] [Google Scholar]
  7. Galanos C., Lüderitz O., Westphal O. A new method for the extraction of R lipopolysaccharides. Eur J Biochem. 1969 Jun;9(2):245–249. doi: 10.1111/j.1432-1033.1969.tb00601.x. [DOI] [PubMed] [Google Scholar]
  8. Galanos C., Lüderitz O., Westphal O. Preparation and properties of antisera against the lipid-A component of bacterial lipopolysaccharides. Eur J Biochem. 1971 Dec 22;24(1):116–122. doi: 10.1111/j.1432-1033.1971.tb19661.x. [DOI] [PubMed] [Google Scholar]
  9. Galanos C. Physical state and biological activity of lipopolysaccharides. Toxicity and immunogenicity of the lipid A component. Z Immunitatsforsch Exp Klin Immunol. 1975 Jul;149(2-4):214–229. [PubMed] [Google Scholar]
  10. Galanos C., Rietschel E. T., Lüderitz O., Westphal O. Interaction of lipopolysaccharides and lipid A with complement. Eur J Biochem. 1971 Mar 1;19(1):143–152. doi: 10.1111/j.1432-1033.1971.tb01298.x. [DOI] [PubMed] [Google Scholar]
  11. Galanos C., Rietschel E. T., Lüderitz O., Westphal O., Kim Y. B., Watson D. W. Biological activities of lipid A complexed with bovine-serum albumin. Eur J Biochem. 1972 Dec 4;31(2):230–233. doi: 10.1111/j.1432-1033.1972.tb02524.x. [DOI] [PubMed] [Google Scholar]
  12. Hanson L. A., Holmgren J., Jodal U., Kaijser B. Characterization of precipitating antibodies to E. coli O antigen in infants and children with acute pyelonephritis. Clin Exp Immunol. 1971 Apr;8(4):573–580. [PMC free article] [PubMed] [Google Scholar]
  13. Hase S., Rietschel E. T. Isolation and analysis of the lipid A backbone. Lipid A structure of lipopolysaccharides from various bacterial groups. Eur J Biochem. 1976 Mar 16;63(1):101–107. doi: 10.1111/j.1432-1033.1976.tb10212.x. [DOI] [PubMed] [Google Scholar]
  14. Holmgren J. The antibody response in rabbits to E. coli K antigen. Int Arch Allergy Appl Immunol. 1970;37(6):638–648. doi: 10.1159/000230252. [DOI] [PubMed] [Google Scholar]
  15. Hämmerling G., Lüderitz O., Westphal O., Mäkelä P. H. Structural investigations on the core polysaccharide of Escherichia coli 0100. Eur J Biochem. 1971 Oct 14;22(3):331–344. doi: 10.1111/j.1432-1033.1971.tb01549.x. [DOI] [PubMed] [Google Scholar]
  16. Irvin R. T., Chatterjee A. K., Sanderson K. E., Costerton J. W. Comparison of the cell envelope structure of a lipopolysaccharide-defective (heptose-deficient) strain and a smooth strain of Salmonella typhimurium. J Bacteriol. 1975 Nov;124(2):930–941. doi: 10.1128/jb.124.2.930-941.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Johns M. A., Bruins S. C., McCabe W. R. Immunization with R mutants of Salmonella minnesota. II. Serological response to lipid A and the lipopolysaccharide of Re mutants. Infect Immun. 1977 Jul;17(1):9–15. doi: 10.1128/iai.17.1.9-15.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kasai N. Chemical studies on the lipid component of endotoxin, with special emphasis on its relation to biological activities. Ann N Y Acad Sci. 1966 Jun 30;133(2):486–507. doi: 10.1111/j.1749-6632.1966.tb52385.x. [DOI] [PubMed] [Google Scholar]
  19. Koplow J., Goldfine H. Alterations in the outer membrane of the cell envelope of heptose-deficient mutants of Escherichia coli. J Bacteriol. 1974 Feb;117(2):527–543. doi: 10.1128/jb.117.2.527-543.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. LAURELL C. B. ANTIGEN-ANTIBODY CROSSED ELECTROPHORESIS. Anal Biochem. 1965 Feb;10:358–361. doi: 10.1016/0003-2697(65)90278-2. [DOI] [PubMed] [Google Scholar]
  21. Lüderitz O., Galanos C., Lehmann V., Rietschel E. T. Recent findings on the chemical structure and biological activity of bacterial lipopolysaccharides. J Hyg Epidemiol Microbiol Immunol. 1974;18(4):381–390. [PubMed] [Google Scholar]
  22. McCabe W. R., Bruins S. C., Craven D. E., Johns M. Cross-reactive antigens: their potential for immunization-induced immunity to Gram-negative bacteria. J Infect Dis. 1977 Aug;136 (Suppl):S161–S166. doi: 10.1093/infdis/136.supplement.s161. [DOI] [PubMed] [Google Scholar]
  23. McCabe W. R. Immunization with R mutants of S. Minnesota. I. Protection against challenge with heterologous gram-negative bacilli. J Immunol. 1972 Mar;108(3):601–610. [PubMed] [Google Scholar]
  24. Mullan N. A., Newsome P. M., Cunnington P. G., Palmer G. H., Wilson M. E. Protection against gram-negative infections with antiserum to lipid A from Salmonella minnesota R595. Infect Immun. 1974 Dec;10(6):1195–1201. doi: 10.1128/iai.10.6.1195-1201.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. NETER E. Bacterial hemagglutination and hemolysis. Bacteriol Rev. 1956 Sep;20(3):166–188. doi: 10.1128/br.20.3.166-188.1956. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. NOWOTNY A. Relation of structure to function in bacterial O antigens. II. Fractionation of lipids present in Boivin-type endotoxin of Serratia marcescens. J Bacteriol. 1963 Feb;85:427–435. doi: 10.1128/jb.85.2.427-435.1963. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Ng A. K., Chen C. L., Chang C. M., Nowotny A. Relationship of structure to function in bacterial endotoxins: serologically cross-reactive components and their effect on protection of mice against some gram-negative infections. J Gen Microbiol. 1976 May;94(1):107–116. doi: 10.1099/00221287-94-1-107. [DOI] [PubMed] [Google Scholar]
  28. Parton R. Envelope proteins in Salmonella minnesota mutants. J Gen Microbiol. 1975 Jul;89(1):113–123. doi: 10.1099/00221287-89-1-113. [DOI] [PubMed] [Google Scholar]
  29. Rietschel E. T., Kim Y. B., Watson D. W., Galanos C., Lüderitz O., Westphal O. Pyrogenicity and immunogenicity of lipid A complexed with bovine serum albumin or human serum albumin. Infect Immun. 1973 Aug;8(2):173–177. doi: 10.1128/iai.8.2.173-177.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rietschel E. T., Lüderitz O. Chemical structure of lipopolysaccharides and endotoxin immunity. Z Immunitatsforsch Exp Klin Immunol. 1975 Jul;149(2-4):201–213. [PubMed] [Google Scholar]
  31. Smit J., Kamio Y., Nikaido H. Outer membrane of Salmonella typhimurium: chemical analysis and freeze-fracture studies with lipopolysaccharide mutants. J Bacteriol. 1975 Nov;124(2):942–958. doi: 10.1128/jb.124.2.942-958.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. WADSWORTH C. A slide microtechnique for the analysis of immune precipitates in gel. Int Arch Allergy Appl Immunol. 1957;10(6):355–360. doi: 10.1159/000228394. [DOI] [PubMed] [Google Scholar]
  33. WARAVDEKAR V. S., SASLAW L. D. A sensitive colorimetric method for the estimation of 2-deoxy sugars with the use of the malonaldehyde-thiobarbituric acid reaction. J Biol Chem. 1959 Aug;234(8):1945–1950. [PubMed] [Google Scholar]
  34. WINBERG J., ANDERSEN H. J., HANSON L. A., LINCOLN K. STUDIES OF URINARY TRACT INFECTIONS IN INFANCY AND CHILDHOOD. I. ANTIBODY RESPONSE IN DIFFERENT TYPES OF URINARY TRACT INFECTIONS CAUSED BY COLIFORM BACTERIA. Br Med J. 1963 Aug 31;2(5356):524–527. doi: 10.1136/bmj.2.5356.524. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Westenfelder M., Galanos C. Experimental lipid A-induced nephritis in the dog. A possible role of lipid A in the pathogenesis of abacterial chronic pyelonephritis. Infection. 1974;2(4):174–177. doi: 10.1007/BF01641456. [DOI] [PubMed] [Google Scholar]
  36. Young L. S., Stevens P., Ingram J. Functional role of antibody against "core" glycolipid of Enterobacteriaceae. J Clin Invest. 1975 Oct;56(4):850–861. doi: 10.1172/JCI108164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ziegler E. J., Douglas H., Sherman J. E., Davis C. E., Braude A. I. Treatment of E. coli and klebsiella bacteremia in agranulocytic animals with antiserum to a UDP-gal epimerase-deficient mutant. J Immunol. 1973 Aug;111(2):433–438. [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES