Skip to main content
PMC home page
Infection and Immunity logoLink to Infection and Immunity
. 1995 May;63(5):1899–1905. doi: 10.1128/iai.63.5.1899-1905.1995

Variation in the structure of glucuronoxylomannan in isolates from patients with recurrent cryptococcal meningitis.

R Cherniak 1, L C Morris 1, T Belay 1, E D Spitzer 1, A Casadevall 1
PMCID: PMC173241  PMID: 7729900

Abstract

Capsular glucuronoxylomannans (GXM) of Cryptococcus neoformans var. neoformans isolates from patients with recurrent cryptococcal meningitis were analyzed by 1H nuclear magnetic resonance spectroscopy and for reactivity with factor sera (Iatron, Tokyo, Japan). For each patient the initial and relapse isolates had previously been shown to be indistinguishable by DNA restriction fragment length polymorphism analysis. For patients J11 and J22 the GXM of the initial and relapse isolates were identical. For patients SB4 and SB6 the GXM of the initial and relapse isolates differed in structure and reactivity with factor sera. In patient SB4 the initial isolate had a serotype A/D structure, and the first relapse isolate had a serotype A structure. The second relapse isolate was a mixture of structures composed of serotype D components, glucuronomannan (GM), and a minor serotype A component. Analysis of the initial isolate from patient SB6 showed a structure composed mainly of serotype D, GM, and minor serotype A components and components not assigned to a particular serotype (N). The relapse isolate had the same composition as the initial isolate except for an increase in the serotype A component. This increase in the serotype A component of the relapse isolate resulted in a change in the serological specificity from serotype D to serotype A/D. The initial isolate from patient J9 had serotype D and GM structures. The first two relapse isolates had serotype D, N, and GM structures and a minor serotype A component. The third relapse isolate had mainly a serotype D structure. All the J9 isolates reacted only with serotype D-specific factor serum. These results indicate that some isolates obtained from patients with recurrent C. neoformans infections have undergone a change in GXM structure during the course of infection. The modification of GXM structure observed in some relapse isolates is reflected in changed serological properties. The results may have important implications for the design of vaccines and antibody-based therapeutic strategies against C. neoformans.

Full Text

The Full Text of this article is available as a PDF (282.9 KB).

Selected References

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

  1. Belay T., Cherniak R. Determination of antigen binding specificities of Cryptococcus neoformans factor sera by enzyme-linked immunosorbent assay. Infect Immun. 1995 May;63(5):1810–1819. doi: 10.1128/iai.63.5.1810-1819.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Belay T., Cherniak R., Shinoda T. Specificity of Cryptococcus neoformans factor sera determined by enzyme-linked immunosorbent assay and dot enzyme assay. Infect Immun. 1993 Jul;61(7):2879–2885. doi: 10.1128/iai.61.7.2879-2885.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhattacharjee A. K., Bennett J. E., Glaudemans C. P. Capsular polysaccharides of Cryptococcus neoformans. Rev Infect Dis. 1984 Sep-Oct;6(5):619–624. doi: 10.1093/clinids/6.5.619. [DOI] [PubMed] [Google Scholar]
  4. Brunham R. C., Plummer F. A., Stephens R. S. Bacterial antigenic variation, host immune response, and pathogen-host coevolution. Infect Immun. 1993 Jun;61(6):2273–2276. doi: 10.1128/iai.61.6.2273-2276.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bulmer G. S., Sans M. D., Gunn C. M. Cryptococcus neoformans. I. Nonencapsulated mutants. J Bacteriol. 1967 Nov;94(5):1475–1479. doi: 10.1128/jb.94.5.1475-1479.1967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Casadevall A., Spitzer E. D., Webb D., Rinaldi M. G. Susceptibilities of serial Cryptococcus neoformans isolates from patients with recurrent cryptococcal meningitis to amphotericin B and fluconazole. Antimicrob Agents Chemother. 1993 Jun;37(6):1383–1386. doi: 10.1128/aac.37.6.1383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cherniak R., Jones R. G., Slodki M. E. Type-specific polysaccharides of Cryptococcus neoformans. n.m.r.-spectral study of a glucuronomannan chemically derived from a Tremella mesenterica exopolysaccharide. Carbohydr Res. 1988 Nov 1;182(2):227–239. doi: 10.1016/0008-6215(88)84005-9. [DOI] [PubMed] [Google Scholar]
  8. Cherniak R., Morris L. C., Anderson B. C., Meyer S. A. Facilitated isolation, purification, and analysis of glucuronoxylomannan of Cryptococcus neoformans. Infect Immun. 1991 Jan;59(1):59–64. doi: 10.1128/iai.59.1.59-64.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Currie B. P., Casadevall A. Estimation of the prevalence of cryptococcal infection among patients infected with the human immunodeficiency virus in New York City. Clin Infect Dis. 1994 Dec;19(6):1029–1033. doi: 10.1093/clinids/19.6.1029. [DOI] [PubMed] [Google Scholar]
  10. Currie B. P., Freundlich L. F., Casadevall A. Restriction fragment length polymorphism analysis of Cryptococcus neoformans isolates from environmental (pigeon excreta) and clinical sources in New York City. J Clin Microbiol. 1994 May;32(5):1188–1192. doi: 10.1128/jcm.32.5.1188-1192.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DROUHET E., SEGRETAIN G. Inhibition de la migration leucocytaire in vitro par un polyoside capsulaire de Torulopsis (Cryptococcus) neoformans. Ann Inst Pasteur (Paris) 1951 Dec;81(6):674–676. [PubMed] [Google Scholar]
  12. Devi S. J., Schneerson R., Egan W., Ulrich T. J., Bryla D., Robbins J. B., Bennett J. E. Cryptococcus neoformans serotype A glucuronoxylomannan-protein conjugate vaccines: synthesis, characterization, and immunogenicity. Infect Immun. 1991 Oct;59(10):3700–3707. doi: 10.1128/iai.59.10.3700-3707.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Dromer F., Charreire J., Contrepois A., Carbon C., Yeni P. Protection of mice against experimental cryptococcosis by anti-Cryptococcus neoformans monoclonal antibody. Infect Immun. 1987 Mar;55(3):749–752. doi: 10.1128/iai.55.3.749-752.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. EVANS E. E. The antigenic composition of Cryptococcus neoformans. I. A serologic classification by means of the capsular and agglutination reactions. J Immunol. 1950 May;64(5):423–430. [PubMed] [Google Scholar]
  15. Ghannoum M. A., Spellberg B. J., Ibrahim A. S., Ritchie J. A., Currie B., Spitzer E. D., Edwards J. E., Jr, Casadevall A. Sterol composition of Cryptococcus neoformans in the presence and absence of fluconazole. Antimicrob Agents Chemother. 1994 Sep;38(9):2029–2033. doi: 10.1128/aac.38.9.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ikeda R., Shinoda T., Fukazawa Y., Kaufman L. Antigenic characterization of Cryptococcus neoformans serotypes and its application to serotyping of clinical isolates. J Clin Microbiol. 1982 Jul;16(1):22–29. doi: 10.1128/jcm.16.1.22-29.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Jacobson E. S., Ayers D. J., Harrell A. C., Nicholas C. C. Genetic and phenotypic characterization of capsule mutants of Cryptococcus neoformans. J Bacteriol. 1982 Jun;150(3):1292–1296. doi: 10.1128/jb.150.3.1292-1296.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Klebanoff S. J. Oxygen metabolism and the toxic properties of phagocytes. Ann Intern Med. 1980 Sep;93(3):480–489. doi: 10.7326/0003-4819-93-3-480. [DOI] [PubMed] [Google Scholar]
  19. Kozel T. R., Gotschlich E. C. The capsule of cryptococcus neoformans passively inhibits phagocytosis of the yeast by macrophages. J Immunol. 1982 Oct;129(4):1675–1680. [PubMed] [Google Scholar]
  20. Kozel T. R., Gulley W. F., Cazin J., Jr Immune response to Cryptococcus neoformans soluble polysaccharide: immunological unresponsiveness. Infect Immun. 1977 Dec;18(3):701–707. doi: 10.1128/iai.18.3.701-707.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Kozel T. R., Pfrommer G. S., Guerlain A. S., Highison B. A., Highison G. J. Role of the capsule in phagocytosis of Cryptococcus neoformans. Rev Infect Dis. 1988 Jul-Aug;10 (Suppl 2):S436–S439. doi: 10.1093/cid/10.supplement_2.s436. [DOI] [PubMed] [Google Scholar]
  22. Kwon-Chung K. J. A new genus, filobasidiella, the perfect state of Cryptococcus neoformans. Mycologia. 1975 Nov-Dec;67(6):1197–1200. [PubMed] [Google Scholar]
  23. Kwon-Chung K. J., Bennett J. E. Epidemiologic differences between the two varieties of Cryptococcus neoformans. Am J Epidemiol. 1984 Jul;120(1):123–130. doi: 10.1093/oxfordjournals.aje.a113861. [DOI] [PubMed] [Google Scholar]
  24. Kwon-Chung K. J., Wickes B. L., Stockman L., Roberts G. D., Ellis D., Howard D. H. Virulence, serotype, and molecular characteristics of environmental strains of Cryptococcus neoformans var. gattii. Infect Immun. 1992 May;60(5):1869–1874. doi: 10.1128/iai.60.5.1869-1874.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Levitz S. M., Dupont M. P. Phenotypic and functional characterization of human lymphocytes activated by interleukin-2 to directly inhibit growth of Cryptococcus neoformans in vitro. J Clin Invest. 1993 Apr;91(4):1490–1498. doi: 10.1172/JCI116354. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Mukherjee J., Scharff M. D., Casadevall A. Protective murine monoclonal antibodies to Cryptococcus neoformans. Infect Immun. 1992 Nov;60(11):4534–4541. doi: 10.1128/iai.60.11.4534-4541.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Murphy J. W., Cozad G. C. Immunological unresponsiveness induced by cryptococcal capsular polysaccharide assayed by the hemolytic plaque technique. Infect Immun. 1972 Jun;5(6):896–901. doi: 10.1128/iai.5.6.896-901.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Murphy J. W., Hidore M. R., Wong S. C. Direct interactions of human lymphocytes with the yeast-like organism, Cryptococcus neoformans. J Clin Invest. 1993 Apr;91(4):1553–1566. doi: 10.1172/JCI116361. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Perfect J. R., Ketabchi N., Cox G. M., Ingram C. W., Beiser C. L. Karyotyping of Cryptococcus neoformans as an epidemiological tool. J Clin Microbiol. 1993 Dec;31(12):3305–3309. doi: 10.1128/jcm.31.12.3305-3309.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Pettoello-Mantovani M., Casadevall A., Kollmann T. R., Rubinstein A., Goldstein H. Enhancement of HIV-1 infection by the capsular polysaccharide of Cryptococcus neoformans. Lancet. 1992 Jan 4;339(8784):21–23. doi: 10.1016/0140-6736(92)90142-p. [DOI] [PubMed] [Google Scholar]
  31. Sanford J. E., Lupan D. M., Schlageter A. M., Kozel T. R. Passive immunization against Cryptococcus neoformans with an isotype-switch family of monoclonal antibodies reactive with cryptococcal polysaccharide. Infect Immun. 1990 Jun;58(6):1919–1923. doi: 10.1128/iai.58.6.1919-1923.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schlageter A. M., Kozel T. R. Opsonization of Cryptococcus neoformans by a family of isotype-switch variant antibodies specific for the capsular polysaccharide. Infect Immun. 1990 Jun;58(6):1914–1918. doi: 10.1128/iai.58.6.1914-1918.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Soll D. R., Galask R., Isley S., Rao T. V., Stone D., Hicks J., Schmid J., Mac K., Hanna C. Switching of Candida albicans during successive episodes of recurrent vaginitis. J Clin Microbiol. 1989 Apr;27(4):681–690. doi: 10.1128/jcm.27.4.681-690.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Spiropulu C., Eppard R. A., Otteson E., Kozel T. R. Antigenic variation within serotypes of Cryptococcus neoformans detected by monoclonal antibodies specific for the capsular polysaccharide. Infect Immun. 1989 Oct;57(10):3240–3242. doi: 10.1128/iai.57.10.3240-3242.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Spitzer E. D., Spitzer S. G. Use of a dispersed repetitive DNA element to distinguish clinical isolates of Cryptococcus neoformans. J Clin Microbiol. 1992 May;30(5):1094–1097. doi: 10.1128/jcm.30.5.1094-1097.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Still C. N., Jacobson E. S. Recombinational mapping of capsule mutations in Cryptococcus neoformans. J Bacteriol. 1983 Oct;156(1):460–462. doi: 10.1128/jb.156.1.460-462.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Sundstrom J. B., Cherniak R. T-cell-dependent and T-cell-independent mechanisms of tolerance to glucuronoxylomannan of Cryptococcus neoformans serotype A. Infect Immun. 1993 Apr;61(4):1340–1345. doi: 10.1128/iai.61.4.1340-1345.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sundstrom J. B., Cherniak R. The glucuronoxylomannan of Cryptococcus neoformans serotype A is a type 2 T-cell-independent antigen. Infect Immun. 1992 Oct;60(10):4080–4087. doi: 10.1128/iai.60.10.4080-4087.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Tsang V. C., Peralta J. M., Simons A. R. Enzyme-linked immunoelectrotransfer blot techniques (EITB) for studying the specificities of antigens and antibodies separated by gel electrophoresis. Methods Enzymol. 1983;92:377–391. doi: 10.1016/0076-6879(83)92032-3. [DOI] [PubMed] [Google Scholar]
  40. Turner S. H., Cherniak R., Reiss E., Kwon-Chung K. J. Structural variability in the glucuronoxylomannan of Cryptococcus neoformans serotype A isolates determined by 13C NMR spectroscopy. Carbohydr Res. 1992 Sep 2;233:205–218. doi: 10.1016/s0008-6215(00)90932-7. [DOI] [PubMed] [Google Scholar]
  41. Wilson D. E., Bennett J. E., Bailey J. W. Serologic grouping of Cryptococcus neoformans. Proc Soc Exp Biol Med. 1968 Mar;127(3):820–823. doi: 10.3181/00379727-127-32812. [DOI] [PubMed] [Google Scholar]
  42. Young B. J., Kozel T. R. Effects of strain variation, serotype, and structural modification on kinetics for activation and binding of C3 to Cryptococcus neoformans. Infect Immun. 1993 Jul;61(7):2966–2972. doi: 10.1128/iai.61.7.2966-2972.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES