Skip to main content
Journal of Clinical Microbiology logoLink to Journal of Clinical Microbiology
. 1996 Jul;34(7):1739–1744. doi: 10.1128/jcm.34.7.1739-1744.1996

Persistence, replacement, and microevolution of Cryptococcus neoformans strains in recurrent meningitis in AIDS patients.

D Sullivan 1, K Haynes 1, G Moran 1, D Shanley 1, D Coleman 1
PMCID: PMC229105  PMID: 8784580

Abstract

Six separate human immunodeficiency virus-positive patients with cryptococcal meningitis were each found to have been infected with a unique strain of Cryptococcus neoformans on the basis of genomic DNA finger-printing analysis with the microsatellite sequence-containing oligonucleotide probe (GGAT)4 and by random amplification of polymorphic DNA. Two patients (A and B) experienced a recurrent episode of infection. Between 12 and 16 single-colony isolates recovered from primary isolation media (> 50% of C. neoformans colonies recovered) from cerebrospinal fluid specimens were fingerprinted from both patients during each episode. The fingerprints of both isolate collections from patient B were very similar, although minor polymorphisms were evident in both sets of profiles. The fingerprints of the isolate collection from the initial episode of infection in patient A were also identical to each other, apart from minor polymorphisms, but they were clearly different from the corresponding profiles of the isolate collection from the recurrent episode, the latter of which were completely identical, apart from minor polymorphisms in a single isolate. Furthermore, prolonged storage and in vitro subculture of the isolates did not alter the fingerprint profiles. These results provided convincing evidence that patients A and B were each infected with a single C. neoformans strain during each episode of infection and that in patient B, the same strain persisted and caused both episodes, while in patient A, a different strain was responsible for each episode. The prevalence of polymorphisms in multiple single-colony isolates from both patients also suggested that C. neoformans populations may undergo microevolution.

Full Text

The Full Text of this article is available as a PDF (590.8 KB).

Selected References

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

  1. 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]
  2. 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]
  3. 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]
  4. Casadevall A., Spitzer E. D. 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 Jun;33(6):1682–1683. doi: 10.1128/jcm.33.6.1682-1683.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Chuck S. L., Sande M. A. Infections with Cryptococcus neoformans in the acquired immunodeficiency syndrome. N Engl J Med. 1989 Sep 21;321(12):794–799. doi: 10.1056/NEJM198909213211205. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. 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]
  9. 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]
  10. Levitz S. M. The ecology of Cryptococcus neoformans and the epidemiology of cryptococcosis. Rev Infect Dis. 1991 Nov-Dec;13(6):1163–1169. doi: 10.1093/clinids/13.6.1163. [DOI] [PubMed] [Google Scholar]
  11. Lockhart S. R., Fritch J. J., Meier A. S., Schröppel K., Srikantha T., Galask R., Soll D. R. Colonizing populations of Candida albicans are clonal in origin but undergo microevolution through C1 fragment reorganization as demonstrated by DNA fingerprinting and C1 sequencing. J Clin Microbiol. 1995 Jun;33(6):1501–1509. doi: 10.1128/jcm.33.6.1501-1509.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Mitchell T. G., Perfect J. R. Cryptococcosis in the era of AIDS--100 years after the discovery of Cryptococcus neoformans. Clin Microbiol Rev. 1995 Oct;8(4):515–548. doi: 10.1128/cmr.8.4.515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Odds F. C., De Backer T., Dams G., Vranckx L., Woestenborghs F. Oxygen as limiting nutrient for growth of Cryptococcus neoformans. J Clin Microbiol. 1995 Apr;33(4):995–997. doi: 10.1128/jcm.33.4.995-997.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. 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]
  16. Polacheck I., Lebens G. A. Electrophoretic karyotype of the pathogenic yeast Cryptococcus neoformans. J Gen Microbiol. 1989 Jan;135(1):65–71. doi: 10.1099/00221287-135-1-65. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. 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]
  19. 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]
  20. Sullivan D., Bennett D., Henman M., Harwood P., Flint S., Mulcahy F., Shanley D., Coleman D. Oligonucleotide fingerprinting of isolates of Candida species other than C. albicans and of atypical Candida species from human immunodeficiency virus-positive and AIDS patients. J Clin Microbiol. 1993 Aug;31(8):2124–2133. doi: 10.1128/jcm.31.8.2124-2133.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Varma A., Kwon-Chung K. J. DNA probe for strain typing of Cryptococcus neoformans. J Clin Microbiol. 1992 Nov;30(11):2960–2967. doi: 10.1128/jcm.30.11.2960-2967.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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