title: Phylogeny and phenotypic characterization of pathogenic Cryptococcus species and closely related saprobic taxa in the Tremellales.
abstract: The basidiomycetous yeasts Cryptococcus neoformans and Cryptococcus gattii are closely related sibling species that cause respiratory and neurological disease in humans and animals. Within these two recognized species, phylogenetic analysis reveals at least six cryptic species defined as molecular types (VNI/II/B, VNIV, VGI, VGII, VGIII, and VGIV) that comprise the pathogenic Cryptococcus species complex. These pathogenic species are clustered in the Filobasidiella clade within the order Tremellales. Previous studies have shown that the Filobasidiella clade also includes several saprobic fungi isolated from insect frass, but information evaluating the relatedness of the saprobes and pathogens within this cluster is limited. Here, the phylogeny encompassing a subset of species in the Tremellales lineage that clusters closely with the pathogenic Cryptococcus species complex was resolved by employing a multilocus sequencing approach for phylogenetic analysis. Six highly conserved genomic loci from 15 related basidiomycete species were sequenced, and the alignments from the concatenated gene sequences were evaluated with different tree-building criteria. Furthermore, these 15 species were subjected to virulence and phenotype assays to evaluate their pathogenic potential. These studies revealed that Cryptococcus amylolentus and Tsuchiyaea wingfieldii, two nonpathogenic sibling species, are the taxa most closely related to the pathogens C. neoformans and C. gattii and together with Filobasidiella depauperata form a Cryptococcus sensu stricto group. Five other saprobic yeast species form the Kwoniella clade, which appears to be a part of a more distantly related sensu lato group. This study establishes a foundation for future comparative genomic approaches that will provide insight into the structure, function, and evolution of the mating type locus, the transitions in modes of sexual reproduction, and the emergence of human pathogenic species from related or ancestral saprobic species.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Keisha
authors.initials: K
authors.lastname: Findley
authors.forename: Marianela
authors.initials: M
authors.lastname: Rodriguez-Carres
authors.forename: Banu
authors.initials: B
authors.lastname: Metin
authors.forename: Johannes
authors.initials: J
authors.lastname: Kroiss
authors.forename: Alvaro
authors.initials: A
authors.lastname: Fonseca
authors.forename: Rytas
authors.initials: R
authors.lastname: Vilgalys
authors.forename: Joseph
authors.initials: J
authors.lastname: Heitman
mesh_terms: D000818:Animals; D001487:Basidiomycota / Q000145:classification* / Q000235:genetics; D003453:Cryptococcosis / Q000382:microbiology*; D003454:Cryptococcus / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification / Q000472:pathogenicity*; D004271:DNA, Fungal / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics; D006801:Humans; D007313:Insecta / Q000382:microbiology*; D008969:Molecular Sequence Data; D016533:Mycological Typing Techniques; D010641:Phenotype; D010802:Phylogeny; D012988:Soil Microbiology; D014774:Virulence
chemical_list: D004271:DNA, Fungal; D004275:DNA, Ribosomal