| Title: | Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates |
| Author(s): | Nielsen K; Cox GM; Wang P; Toffaletti DL; Perfect JR; Heitman J; |
| Address: | "Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA" |
| DOI: | 10.1128/IAI.71.9.4831-4841.2003 |
| ISSN/ISBN: | 0019-9567 (Print) 1098-5522 (Electronic) 0019-9567 (Linking) |
| Abstract: | "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" |
| Keywords: | "Animals Base Sequence Cryptococcus neoformans/genetics/isolation & purification/*pathogenicity/*physiology DNA, Fungal/genetics Female Genes, Fungal Genes, Mating Type, Fungal Haploidy Humans Male Meningitis, Cryptococcal/etiology/microbiology Mice Mice, ;" |
| Notes: | "MedlineNielsen, Kirsten Cox, Gary M Wang, Ping Toffaletti, Dena L Perfect, John R Heitman, Joseph eng AI50113/AI/NIAID NIH HHS/ R01 AI028388/AI/NIAID NIH HHS/ R01 AI050113/AI/NIAID NIH HHS/ R01 AI28388/AI/NIAID NIH HHS/ AI44975/AI/NIAID NIH HHS/ P01 AI044975/AI/NIAID NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 2003/08/23 Infect Immun. 2003 Sep; 71(9):4831-41. doi: 10.1128/IAI.71.9.4831-4841.2003" |
