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. 1995 Jan;63(1):21–26. doi: 10.1128/iai.63.1.21-26.1995

Biologic activities of antibodies to the neutral-polysaccharide component of the Pseudomonas aeruginosa lipopolysaccharide are blocked by O side chains and mucoid exopolysaccharide (alginate).

K Hatano 1, J B Goldberg 1, G B Pier 1
PMCID: PMC172952  PMID: 7528730

Abstract

Virulent strains of Pseudomonas aeruginosa are either of a nonmucoid, lipopolysaccharide (LPS)-smooth or mucoid, LPS-rough phenotype, and immunity to these different variants is efficiently mediated by antibodies specific to O antigens or mucoid exopolysaccharide (also called alginate), respectively. In addition to O side chains and core polysaccharide components, the LPS of P. aeruginosa also contains neutral-polysaccharide components that express antigenic determinants common to many clinical isolates. We evaluated antibodies specific to neutral polysaccharides for the ability to mediate opsonic killing and protective immunity. Antibodies to these antigens mediated opsonic killing of poorly virulent nonmucoid LPS-rough isolates but not of isogenic strains with either a LPS-smooth or a mucoid phenotype. Antibodies to neutral-polysaccharide antigens also failed to protect neutropenic mice from challenge with modest doses of LPS-smooth P. aeruginosa strains (< 10(3) CFU per mouse), whereas O-antigen-specific antibodies were highly protective. Antibodies to neutral polysaccharides deposited significantly (P = 0.002) more C3 onto LPS-rough strains than did antibodies to O side chains, but this situation was reversed when isogenic LPS-smooth strains were tested. Given that protective immunity against P. aeruginosa must be directed against either nonmucoid LPS-smooth strains or mucoid LPS-rough strains, it appears that antibodies specific to neutral-polysaccharide antigens do not protect against P. aeruginosa infection. Lack of protection is likely due to the ability of both O side chains and mucoid exopolysaccharide (alginate) to interfere with the opsonic killing activity of neutral-polysaccharide-specific antibodies.

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Selected References

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  1. Ames P., DesJardins D., Pier G. B. Opsonophagocytic killing activity of rabbit antibody to Pseudomonas aeruginosa mucoid exopolysaccharide. Infect Immun. 1985 Aug;49(2):281–285. doi: 10.1128/iai.49.2.281-285.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown E. J., Joiner K. A., Frank M. M. The role of complement in host resistance to bacteria. Springer Semin Immunopathol. 1983;6(4):349–360. doi: 10.1007/BF02116279. [DOI] [PubMed] [Google Scholar]
  3. Cryz S. J., Jr, Fürer E., Germanier R. Passive protection against Pseudomonas aeruginosa infection in an experimental leukopenic mouse model. Infect Immun. 1983 May;40(2):659–664. doi: 10.1128/iai.40.2.659-664.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cryz S. J., Jr, Fürer E., Germanier R. Protection against fatal Pseudomonas aeruginosa burn wound sepsis by immunization with lipopolysaccharide and high-molecular-weight polysaccharide. Infect Immun. 1984 Mar;43(3):795–799. doi: 10.1128/iai.43.3.795-799.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cryz S. J., Jr, Fürer E., Germanier R. Simple model for the study of Pseudomonas aeruginosa infections in leukopenic mice. Infect Immun. 1983 Mar;39(3):1067–1071. doi: 10.1128/iai.39.3.1067-1071.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cryz S. J., Jr, Pitt T. L., Fürer E., Germanier R. Role of lipopolysaccharide in virulence of Pseudomonas aeruginosa. Infect Immun. 1984 May;44(2):508–513. doi: 10.1128/iai.44.2.508-513.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Evans D. J., Pier G. B., Coyne M. J., Jr, Goldberg J. B. The rfb locus from Pseudomonas aeruginosa strain PA103 promotes the expression of O antigen by both LPS-rough and LPS-smooth isolates from cystic fibrosis patients. Mol Microbiol. 1994 Aug;13(3):427–434. doi: 10.1111/j.1365-2958.1994.tb00437.x. [DOI] [PubMed] [Google Scholar]
  8. Finke M., Muth G., Reichhelm T., Thoma M., Duchêne M., Hungerer K. D., Domdey H., von Specht B. U. Protection of immunosuppressed mice against infection with Pseudomonas aeruginosa by recombinant P. aeruginosa lipoprotein I and lipoprotein I-specific monoclonal antibodies. Infect Immun. 1991 Apr;59(4):1251–1254. doi: 10.1128/iai.59.4.1251-1254.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gilleland H. E., Gilleland L. B., Fowler M. R. Vaccine efficacies of elastase, exotoxin A, and outer-membrane protein F in preventing chronic pulmonary infection by Pseudomonas aeruginosa in a rat model. J Med Microbiol. 1993 Feb;38(2):79–86. doi: 10.1099/00222615-38-2-79. [DOI] [PubMed] [Google Scholar]
  10. Goldberg J. B., Hatano K., Meluleni G. S., Pier G. B. Cloning and surface expression of Pseudomonas aeruginosa O antigen in Escherichia coli. Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10716–10720. doi: 10.1073/pnas.89.22.10716. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Goldberg J. B., Ohman D. E. Cloning and expression in Pseudomonas aeruginosa of a gene involved in the production of alginate. J Bacteriol. 1984 Jun;158(3):1115–1121. doi: 10.1128/jb.158.3.1115-1121.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gordon D. L., Rice J., Finlay-Jones J. J., McDonald P. J., Hostetter M. K. Analysis of C3 deposition and degradation on bacterial surfaces after opsonization. J Infect Dis. 1988 Apr;157(4):697–704. doi: 10.1093/infdis/157.4.697. [DOI] [PubMed] [Google Scholar]
  13. Hatano K., Goldberg J. B., Pier G. B. Pseudomonas aeruginosa lipopolysaccharide: evidence that the O side chains and common antigens are on the same molecule. J Bacteriol. 1993 Aug;175(16):5117–5128. doi: 10.1128/jb.175.16.5117-5128.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Knirel Y. A. Polysaccharide antigens of Pseudomonas aeruginosa. Crit Rev Microbiol. 1990;17(4):273–304. doi: 10.3109/10408419009105729. [DOI] [PubMed] [Google Scholar]
  15. Kocharova N. A., Hatano K., Shaskov A. S., Knirel Y. A., Kochetkov N. K., Pier G. B. The structure and serologic distribution of an extracellular neutral polysaccharide from Pseudomonas aeruginosa immunotype 3. J Biol Chem. 1989 Sep 15;264(26):15569–15573. [PubMed] [Google Scholar]
  16. Kocharova N. A., Knirel' Iu A., Kochetkov N. K., Stanislavskii E. S. Kharakteristika ramnana, vydelennogo iz preparatov lipopolisakharidov Pseudomonas aeruginosa. Bioorg Khim. 1988 May;14(5):701–703. [PubMed] [Google Scholar]
  17. Kocharova N. A., Knirel Y. A., Shashkov A. S., Kochetkov N. K., Pier G. B. Structure of an extracellular cross-reactive polysaccharide from Pseudomonas aeruginosa immunotype 4. J Biol Chem. 1988 Aug 15;263(23):11291–11295. [PubMed] [Google Scholar]
  18. Kropinski A. M., Chan L. C., Milazzo F. H. The extraction and analysis of lipopolysaccharides from Pseudomonas aeruginosa strain PAO, and three rough mutants. Can J Microbiol. 1979 Mar;25(3):390–398. doi: 10.1139/m79-060. [DOI] [PubMed] [Google Scholar]
  19. Lam J. S., Handelsman M. Y., Chivers T. R., MacDonald L. A. Monoclonal antibodies as probes to examine serotype-specific and cross-reactive epitopes of lipopolysaccharides from serotypes O2, O5, and O16 of Pseudomonas aeruginosa. J Bacteriol. 1992 Apr;174(7):2178–2184. doi: 10.1128/jb.174.7.2178-2184.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lam M. Y., McGroarty E. J., Kropinski A. M., MacDonald L. A., Pedersen S. S., Høiby N., Lam J. S. Occurrence of a common lipopolysaccharide antigen in standard and clinical strains of Pseudomonas aeruginosa. J Clin Microbiol. 1989 May;27(5):962–967. doi: 10.1128/jcm.27.5.962-967.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lightfoot J., Lam J. S. Chromosomal mapping, expression and synthesis of lipopolysaccharide in Pseudomonas aeruginosa: a role for guanosine diphospho (GDP)-D-mannose. Mol Microbiol. 1993 May;8(4):771–782. doi: 10.1111/j.1365-2958.1993.tb01620.x. [DOI] [PubMed] [Google Scholar]
  22. Markham R. B., Pier G. B. Immunologic basis for mouse protection provided by high-molecular-weight polysaccharide from immunotype 1 Pseudomonas aeruginosa. Rev Infect Dis. 1983 Nov-Dec;5 (Suppl 5):S957–S962. doi: 10.1093/clinids/5.supplement_5.s957. [DOI] [PubMed] [Google Scholar]
  23. Oishi K., Sonoda F., Iwagaki A., Ponglertnapagorn P., Watanabe K., Nagatake T., Siadak A., Pollack M., Matsumoto K. Therapeutic effects of a human antiflagella monoclonal antibody in a neutropenic murine model of Pseudomonas aeruginosa pneumonia. Antimicrob Agents Chemother. 1993 Feb;37(2):164–170. doi: 10.1128/aac.37.2.164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Pier G. B., Grout M., Desjardins D. Complement deposition by antibodies to Pseudomonas aeruginosa mucoid exopolysaccharide (MEP) and by non-MEP specific opsonins. J Immunol. 1991 Sep 15;147(6):1869–1876. [PubMed] [Google Scholar]
  25. Pier G. B., Koles N. L., Meluleni G., Hatano K., Pollack M. Specificity and function of murine monoclonal antibodies and immunization-induced human polyclonal antibodies to lipopolysaccharide subtypes of Pseudomonas aeruginosa serogroup 06. Infect Immun. 1994 Apr;62(4):1137–1143. doi: 10.1128/iai.62.4.1137-1143.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Pier G. B. Safety and immunogenicity of high molecular weight polysaccharide vaccine from immunotype 1 Pseudomonas aeruginosa. J Clin Invest. 1982 Feb;69(2):303–308. doi: 10.1172/JCI110453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Pier G. B., Saunders J. M., Ames P., Edwards M. S., Auerbach H., Goldfarb J., Speert D. P., Hurwitch S. Opsonophagocytic killing antibody to Pseudomonas aeruginosa mucoid exopolysaccharide in older noncolonized patients with cystic fibrosis. N Engl J Med. 1987 Sep 24;317(13):793–798. doi: 10.1056/NEJM198709243171303. [DOI] [PubMed] [Google Scholar]
  28. Pier G. B., Small G. J., Warren H. B. Protection against mucoid Pseudomonas aeruginosa in rodent models of endobronchial infections. Science. 1990 Aug 3;249(4968):537–540. doi: 10.1126/science.2116663. [DOI] [PubMed] [Google Scholar]
  29. Pier G. B., Thomas D. M. Lipopolysaccharide and high-molecular-weight polysaccharide serotypes of Pseudomonas aeruginosa. J Infect Dis. 1982 Feb;145(2):217–223. doi: 10.1093/infdis/145.2.217. [DOI] [PubMed] [Google Scholar]
  30. Pier G. B., Thomas D., Small G., Siadak A., Zweerink H. In vitro and in vivo activity of polyclonal and monoclonal human immunoglobulins G, M, and A against Pseudomonas aeruginosa lipopolysaccharide. Infect Immun. 1989 Jan;57(1):174–179. doi: 10.1128/iai.57.1.174-179.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Pollack M., Tao M., Akiyama M., Pier G. B., Koles N. L. In vitro and in vivo functional activities of monoclonal antibodies reactive with Pseudomonas aeruginosa serogroup 6 lipopolysaccharides. Antibiot Chemother (1971) 1991;44:163–171. doi: 10.1159/000420311. [DOI] [PubMed] [Google Scholar]
  32. Pollack M., Young L. S. Protective activity of antibodies to exotoxin A and lipopolysaccharide at the onset of Pseudomonas aeruginosa septicemia in man. J Clin Invest. 1979 Feb;63(2):276–286. doi: 10.1172/JCI109300. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Rivera M., Bryan L. E., Hancock R. E., McGroarty E. J. Heterogeneity of lipopolysaccharides from Pseudomonas aeruginosa: analysis of lipopolysaccharide chain length. J Bacteriol. 1988 Feb;170(2):512–521. doi: 10.1128/jb.170.2.512-521.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Rivera M., McGroarty E. J. Analysis of a common-antigen lipopolysaccharide from Pseudomonas aeruginosa. J Bacteriol. 1989 Apr;171(4):2244–2248. doi: 10.1128/jb.171.4.2244-2248.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rosok M. J., Stebbins M. R., Connelly K., Lostrom M. E., Siadak A. W. Generation and characterization of murine antiflagellum monoclonal antibodies that are protective against lethal challenge with Pseudomonas aeruginosa. Infect Immun. 1990 Dec;58(12):3819–3828. doi: 10.1128/iai.58.12.3819-3828.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Sawada S., Kawamura T., Masuho Y., Tomibe K. A new common polysaccharide antigen of strains of Pseudomonas aeruginosa detected with a monoclonal antibody. J Infect Dis. 1985 Dec;152(6):1290–1299. doi: 10.1093/infdis/152.6.1290. [DOI] [PubMed] [Google Scholar]
  37. Terashima M., Uezumi I., Tomio T., Kato M., Irie K., Okuda T., Yokota S., Noguchi H. A protective human monoclonal antibody directed to the outer core region of Pseudomonas aeruginosa lipopolysaccharide. Infect Immun. 1991 Jan;59(1):1–6. doi: 10.1128/iai.59.1.1-6.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Yokota S., Kaya S., Araki Y., Ito E., Kawamura T., Sawada S. Occurrence of D-rhamnan as the common antigen reactive against monoclonal antibody E87 in Pseudomonas aeruginosa IFO 3080 and other strains. J Bacteriol. 1990 Oct;172(10):6162–6164. doi: 10.1128/jb.172.10.6162-6164.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Yokota S., Kaya S., Sawada S., Kawamura T., Araki Y., Ito E. Characterization of a polysaccharide component of lipopolysaccharide from Pseudomonas aeruginosa IID 1008 (ATCC 27584) as D-rhamnan. Eur J Biochem. 1987 Sep 1;167(2):203–209. doi: 10.1111/j.1432-1033.1987.tb13324.x. [DOI] [PubMed] [Google Scholar]
  40. Yokota S., Terashima M., Chiba J., Noguchi H. Variable cross-reactivity of Pseudomonas aeruginosa lipopolysaccharide-code-specific monoclonal antibodies and its possible relationship with serotype. J Gen Microbiol. 1992 Feb;138(2):289–296. doi: 10.1099/00221287-138-2-289. [DOI] [PubMed] [Google Scholar]

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