@entity1327 is a @entity1 -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 ( @entity1327 . neoformans, serotype D, and @entity14851 , serotypes B and C), yet the vast majority of @entity281 involve a distinct variety ( @entity11937 , 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 @entity5681 . This meiotic segregant was used to create congenic a and alpha mating type serotype A strains. Virulence tests with @entity95 and @entity19 models of @entity1330 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 @entity1 fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.

Sexual cycle of XXXX and virulence of congenic a and alpha isolates.

@entity1 :: ('9606', 'Species') :: ['human'] @entity19 :: ('10090', 'Species') :: ['murine'] @entity1330 :: ('MESH:D016919', 'Disease') :: ['cryptococcal meningitis'] @entity1327 :: ('5207', 'Species') :: ['C. neoformans var', 'Cryptococcus neoformans'] @entity95 :: ('9986', 'Species') :: ['rabbit'] @entity281 :: ('MESH:D007239', 'Disease') :: ['infections'] @entity11937 :: ('178876', 'Species') :: ['C. neoformans var. grubii'] @entity14851 :: ('552467', 'Species') :: ['C. neoformans var. gattii'] @entity5681 :: ('CHEBI:26013', 'Chemical') :: ['pheromone']
@entity11937 :: (178876,Species) :: ['Cryptococcus neoformans var. grubii']
