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Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.

Publication ,  Journal Article
Nielsen, K; Cox, GM; Wang, P; Toffaletti, DL; Perfect, JR; Heitman, J
Published in: Infect Immun
September 2003

Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and alpha mating types has been reported for two varieties (C. neoformans var. neoformans, serotype D, and C. neoformans var. gattii, serotypes B and C), yet the vast majority of infections involve a distinct variety (C. neoformans var. grubii, serotype A) that has been thought to be clonal and restricted to the alpha mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a crg1 mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and alpha mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and alpha mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the alpha mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.

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Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

September 2003

Volume

71

Issue

9

Start / End Page

4831 / 4841

Location

United States

Related Subject Headings

  • Virulence
  • Serotyping
  • Recombination, Genetic
  • Rabbits
  • Opportunistic Infections
  • Mutation
  • Molecular Sequence Data
  • Microbiology
  • Mice, Inbred A
  • Mice
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Nielsen, K., Cox, G. M., Wang, P., Toffaletti, D. L., Perfect, J. R., & Heitman, J. (2003). Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates. Infect Immun, 71(9), 4831–4841. https://doi.org/10.1128/IAI.71.9.4831-4841.2003
Nielsen, Kirsten, Gary M. Cox, Ping Wang, Dena L. Toffaletti, John R. Perfect, and Joseph Heitman. “Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.Infect Immun 71, no. 9 (September 2003): 4831–41. https://doi.org/10.1128/IAI.71.9.4831-4841.2003.
Nielsen K, Cox GM, Wang P, Toffaletti DL, Perfect JR, Heitman J. Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates. Infect Immun. 2003 Sep;71(9):4831–41.
Nielsen, Kirsten, et al. “Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.Infect Immun, vol. 71, no. 9, Sept. 2003, pp. 4831–41. Pubmed, doi:10.1128/IAI.71.9.4831-4841.2003.
Nielsen K, Cox GM, Wang P, Toffaletti DL, Perfect JR, Heitman J. Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates. Infect Immun. 2003 Sep;71(9):4831–4841.

Published In

Infect Immun

DOI

ISSN

0019-9567

Publication Date

September 2003

Volume

71

Issue

9

Start / End Page

4831 / 4841

Location

United States

Related Subject Headings

  • Virulence
  • Serotyping
  • Recombination, Genetic
  • Rabbits
  • Opportunistic Infections
  • Mutation
  • Molecular Sequence Data
  • Microbiology
  • Mice, Inbred A
  • Mice