title: Cryptococcus neoformans STE12alpha regulates virulence but is not essential for mating.
abstract: The Cryptococcus neoformans STE12alpha gene, a homologue of Saccharomyces cerevisiae STE12, exists only in mating type (MAT)alpha cells. In S. cerevisiae, STE12 was required for mating and filament formation. In C. neoformans, haploid fruiting on filament agar required STE12alpha. The ability to form hyphae, however, was not affected by deletion of STE12alpha when convergently growing MATa strains were present. Furthermore, ste12alpha disruptants were fertile when mated with MATa strains, albeit with reduced mating frequency. Most importantly, the virulence of a ste12alpha disruptant of serotype D strain was significantly reduced in a mouse model. When the ste12alpha locus was reconstituted with the wild-type allele by cotransformation, virulence was restored. Histopathological analysis demonstrated a reduction in capsular size of yeast cells, less severe cystic lesions, and stronger immune responses in meninges of mice infected with ste12alpha cells than those of mice infected with STE12alpha cells. Using reporter gene constructs, we found that STE12alpha controls the expression of several phenotypes known to be involved in virulence, such as capsule and melanin production. These results demonstrate a clear molecular link between mating type and virulence in C. neoformans.
authors.affiliation: Laboratory of Clinical Investigation, National Institute of Allergy and Infectious Diseases, Office of the Director, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Y C
authors.initials: YC
authors.lastname: Chang
authors.forename: B L
authors.initials: BL
authors.lastname: Wickes
authors.forename: G F
authors.initials: GF
authors.lastname: Miller
authors.forename: L A
authors.initials: LA
authors.lastname: Penoyer
authors.forename: K J
authors.initials: KJ
authors.lastname: Kwon-Chung
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D003455:Cryptococcus neoformans / Q000145:classification / Q000235:genetics / Q000472:pathogenicity*; D005656:Fungal Proteins / Q000235:genetics*; D006238:Haploidy; D016919:Meningitis, Cryptococcal / Q000401:mortality; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D012098:Reproduction; D029701:Saccharomyces cerevisiae Proteins; D017384:Sequence Deletion; D012703:Serotyping; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D005656:Fungal Proteins; C489241:STE12 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors