Skip to main content
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1996 Apr;34(4):912–917. doi: 10.1128/jcm.34.4.912-917.1996

Molecular subtype distribution of Cryptococcus neoformans in four areas of the United States. Cryptococcal Disease Active Surveillance Group.

M E Brandt 1, L C Hutwagner 1, L A Klug 1, W S Baughman 1, D Rimland 1, E A Graviss 1, R J Hamill 1, C Thomas 1, P G Pappas 1, A L Reingold 1, R W Pinner 1
PMCID: PMC228916  PMID: 8815107

Abstract

To improve understanding of the epidemiology of cryptococcal disease, we analyzed the multilocus genotype distribution of 358 Cryptococcus neoformans isolates obtained from 251 patients through active surveillance in four U.S. geographic areas from 1992 through 1994. Isolates of the predominant enzyme electrophoretic type (ET), ET-1, were recovered in significantly greater proportion from Atlanta, Ga., Houston, Tex., and all major metropolitan areas of Alabama than from San Francisco, Calif. ET-2 and ET-7 complex (serotype AD) isolates were recovered predominantly from San Francisco. ET-3 was recovered less frequently from San Francisco than from the three other locations. These findings may reflect geographic differences in exposure to environmental strains or the identification of previously unrecognized C. neoformans clusters. Analysis by random amplified polymorphic DNA-PCR subtyping further divided 67 ET-1 isolates into 19 additional subtypes, none of which could be associated with a particular geographic region. Multiple isolates from the same patient always revealed the same multilocus enzyme electrophoresis and random amplified polymorphic DNA subtypes. No differences in subtype distribution were found when isolates from AIDS patients were compared with those from persons without or with another underlying disease, although one C. noeformans var. gattii isolate was obtained from an AIDS patient. When body site distribution was analyzed, ET-4 was disproportionately recovered from skin or surface body sites. Evidence for linkage disequilibrium in this fungal population suggests that virulent C. neoformans possesses a clonal population structure. Continued application of molecular subtyping methods will be useful in tracking the source, transmission, and relative virulence of different C. neoformans strains.

Full Text

The Full Text of this article is available as a PDF (179.3 KB).

Selected References

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

  1. Bennett J. E., Kwon-Chung K. J., Howard D. H. Epidemiologic differences among serotypes of Cryptococcus neoformans. Am J Epidemiol. 1977 Jun;105(6):582–586. doi: 10.1093/oxfordjournals.aje.a112423. [DOI] [PubMed] [Google Scholar]
  2. Bibb W. F., Gellin B. G., Weaver R., Schwartz B., Plikaytis B. D., Reeves M. W., Pinner R. W., Broome C. V. Analysis of clinical and food-borne isolates of Listeria monocytogenes in the United States by multilocus enzyme electrophoresis and application of the method to epidemiologic investigations. Appl Environ Microbiol. 1990 Jul;56(7):2133–2141. doi: 10.1128/aem.56.7.2133-2141.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brandt M. E., Bragg S. L., Pinner R. W. Multilocus enzyme typing of Cryptococcus neoformans. J Clin Microbiol. 1993 Oct;31(10):2819–2823. doi: 10.1128/jcm.31.10.2819-2823.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brandt M. E., Hutwagner L. C., Kuykendall R. J., Pinner R. W. Comparison of multilocus enzyme electrophoresis and random amplified polymorphic DNA analysis for molecular subtyping of Cryptococcus neoformans. The Cryplococcal Disease Active Surveillance Group. J Clin Microbiol. 1995 Jul;33(7):1890–1895. doi: 10.1128/jcm.33.7.1890-1895.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Casadevall A., Freundlich L. F., Marsh L., Scharff M. D. Extensive allelic variation in Cryptococcus neoformans. J Clin Microbiol. 1992 May;30(5):1080–1084. doi: 10.1128/jcm.30.5.1080-1084.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Caugant D. A., Sandven P. Epidemiological analysis of Candida albicans strains by multilocus enzyme electrophoresis. J Clin Microbiol. 1993 Feb;31(2):215–220. doi: 10.1128/jcm.31.2.215-220.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chen F., Currie B. P., Chen L. C., Spitzer S. G., Spitzer E. D., Casadevall A. Genetic relatedness of Cryptococcus neoformans clinical isolates grouped with the repetitive DNA probe CNRE-1. J Clin Microbiol. 1995 Nov;33(11):2818–2822. doi: 10.1128/jcm.33.11.2818-2822.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Clancy M. N., Fleischmann J., Howard D. H., Kwon-Chung K. J., Shimizu R. Y. Isolation of Cryptococcus neoformans gattii from a patient with AIDS in southern California. J Infect Dis. 1990 Apr;161(4):809–809. doi: 10.1093/infdis/161.4.809. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Dromer F., Varma A., Ronin O., Mathoulin S., Dupont B. Molecular typing of Cryptococcus neoformans serotype D clinical isolates. J Clin Microbiol. 1994 Oct;32(10):2364–2371. doi: 10.1128/jcm.32.10.2364-2371.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Durden F. M., Elewski B. Cutaneous involvement with Cryptococcus neoformans in AIDS. J Am Acad Dermatol. 1994 May;30(5 Pt 2):844–848. doi: 10.1016/s0190-9622(94)70094-x. [DOI] [PubMed] [Google Scholar]
  12. Grant I. H., Armstrong D. Fungal infections in AIDS. Cryptococcosis. Infect Dis Clin North Am. 1988 Jun;2(2):457–464. [PubMed] [Google Scholar]
  13. Haynes K. A., Sullivan D. J., Coleman D. C., Clarke J. C., Emilianus R., Atkinson C., Cann K. J. Involvement of multiple Cryptococcus neoformans strains in a single episode of cryptococcosis and reinfection with novel strains in recurrent infection demonstrated by random amplification of polymorphic DNA and DNA fingerprinting. J Clin Microbiol. 1995 Jan;33(1):99–102. doi: 10.1128/jcm.33.1.99-102.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kapend'a K., Komichelo K., Swinne D., Vandepitte J. Meningitis due to Cryptococcus neoformans biovar gattii in a Zairean AIDS patient. Eur J Clin Microbiol. 1987 Jun;6(3):320–321. doi: 10.1007/BF02017627. [DOI] [PubMed] [Google Scholar]
  15. Kovacs J. A., Kovacs A. A., Polis M., Wright W. C., Gill V. J., Tuazon C. U., Gelmann E. P., Lane H. C., Longfield R., Overturf G. Cryptococcosis in the acquired immunodeficiency syndrome. Ann Intern Med. 1985 Oct;103(4):533–538. doi: 10.7326/0003-4819-103-4-533. [DOI] [PubMed] [Google Scholar]
  16. 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]
  17. Meyer W., Mitchell T. G., Freedman E. Z., Vilgalys R. Hybridization probes for conventional DNA fingerprinting used as single primers in the polymerase chain reaction to distinguish strains of Cryptococcus neoformans. J Clin Microbiol. 1993 Sep;31(9):2274–2280. doi: 10.1128/jcm.31.9.2274-2280.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mukherjee J., Scharff M. D., Casadevall A. Variable efficacy of passive antibody administration against diverse Cryptococcus neoformans strains. Infect Immun. 1995 Sep;63(9):3353–3359. doi: 10.1128/iai.63.9.3353-3359.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Panther L. A., Sande M. A. Cryptococcal meningitis in the acquired immunodeficiency syndrome. Semin Respir Infect. 1990 Jun;5(2):138–145. [PubMed] [Google Scholar]
  20. Perfect J. R. Cryptococcosis. Infect Dis Clin North Am. 1989 Mar;3(1):77–102. [PubMed] [Google Scholar]
  21. 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]
  22. Pinner R. W., Hajjeh R. A., Powderly W. G. Prospects for preventing cryptococcosis in persons infected with human immunodeficiency virus. Clin Infect Dis. 1995 Aug;21 (Suppl 1):S103–S107. doi: 10.1093/clinids/21.supplement_1.s103. [DOI] [PubMed] [Google Scholar]
  23. Polacheck I., Lebens G., Hicks J. B. Development of DNA probes for early diagnosis and epidemiological study of cryptococcosis in AIDS patients. J Clin Microbiol. 1992 Apr;30(4):925–930. doi: 10.1128/jcm.30.4.925-930.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rozenbaum R., Gonçalves A. J., Wanke B., Vieira W. Cryptococcus neoformans var. gattii in a Brazilian AIDS patients. Mycopathologia. 1990 Oct;112(1):33–34. doi: 10.1007/BF01795177. [DOI] [PubMed] [Google Scholar]
  25. Selander R. K., Caugant D. A., Ochman H., Musser J. M., Gilmour M. N., Whittam T. S. Methods of multilocus enzyme electrophoresis for bacterial population genetics and systematics. Appl Environ Microbiol. 1986 May;51(5):873–884. doi: 10.1128/aem.51.5.873-884.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Spitzer E. D., Spitzer S. G., Freundlich L. F., Casadevall A. Persistence of initial infection in recurrent Cryptococcus neoformans meningitis. Lancet. 1993 Mar 6;341(8845):595–596. doi: 10.1016/0140-6736(93)90354-j. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. St-Germain G., Noël G., Chung K. J. Disseminated cryptococcosis due to Cryptococcus neoformans variety gattii in a Canadian patient with AIDS. Eur J Clin Microbiol Infect Dis. 1988 Aug;7(4):587–588. doi: 10.1007/BF01962626. [DOI] [PubMed] [Google Scholar]
  29. Sugar A. M. Overview: cryptococcosis in the patient with AIDS. Mycopathologia. 1991 Jun;114(3):153–157. doi: 10.1007/BF00437205. [DOI] [PubMed] [Google Scholar]
  30. Tibayrenc M., Kjellberg F., Arnaud J., Oury B., Brenière S. F., Dardé M. L., Ayala F. J. Are eukaryotic microorganisms clonal or sexual? A population genetics vantage. Proc Natl Acad Sci U S A. 1991 Jun 15;88(12):5129–5133. doi: 10.1073/pnas.88.12.5129. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Varma A., Kwon-Chung K. J. Restriction fragment polymorphism in mitochondrial DNA of Cryptococcus neoformans. J Gen Microbiol. 1989 Dec;135(12):3353–3362. doi: 10.1099/00221287-135-12-3353. [DOI] [PubMed] [Google Scholar]
  32. Varma A., Swinne D., Staib F., Bennett J. E., Kwon-Chung K. J. Diversity of DNA fingerprints in Cryptococcus neoformans. J Clin Microbiol. 1995 Jul;33(7):1807–1814. doi: 10.1128/jcm.33.7.1807-1814.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Microbiology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES