title: Investigation of the basis of virulence in serotype A strains of Cryptococcus neoformans from apparently immunocompetent individuals.
abstract: Cryptococcus neoformans serotype A strains commonly infect immunocompromised patients to cause fungal meningitis. To understand the basis of serotype A cryptococcal infections in apparently immunocompetent patients, we tested two hypotheses: the strains were naturally occurring hypervirulent pkr1 (PKA regulatory subunit) mutants, or the strains were hybrids with C. neoformans var. gattii strains that normally infect immunocompetent individuals. Analysis of clinical isolates obtained from apparently immunocompetent individuals from three continents revealed that none were pkr1 mutants, but several exhibited phenotypes consistent with perturbations in cAMP signaling. Additionally, none of the strains were unusual hybrids with gattii strains. Except for one strain that was an AD hybrid, all others were serotype A (var. grubii) isolates. Taken together, our findings indicate that the ability of these clinical isolates to infect apparently normal individuals may be attributable to mutations other than pkr1 and/or underlying immune system impairment in patients.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, USA.
authors.forename: Cletus A
authors.initials: CA
authors.lastname: D'Souza
authors.forename: Ferry
authors.initials: F
authors.lastname: Hagen
authors.forename: Teun
authors.initials: T
authors.lastname: Boekhout
authors.forename: Gary M
authors.initials: GM
authors.lastname: Cox
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D015139:Blotting, Southern; D016000:Cluster Analysis; D003455:Cryptococcus neoformans / Q000235:genetics / Q000472:pathogenicity*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics; D017931:DNA Primers; D005816:Genetic Complementation Test; D006801:Humans; D006824:Hybridization, Genetic; D007121:Immunocompetence / Q000276:immunology*; D016921:Meningitis, Fungal / Q000235:genetics* / Q000276:immunology*; D021141:Nucleic Acid Amplification Techniques; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012150:Polymorphism, Restriction Fragment Length; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D012703:Serotyping; D013045:Species Specificity; D014774:Virulence
chemical_list: D017931:DNA Primers; D017868:Cyclic AMP-Dependent Protein Kinases