title: Whole genome sequence analysis of Cryptococcus gattii from the Pacific Northwest reveals unexpected diversity.
abstract: A recent emergence of Cryptococcus gattii in the Pacific Northwest involves strains that fall into three primarily clonal molecular subtypes: VGIIa, VGIIb and VGIIc. Multilocus sequence typing (MLST) and variable number tandem repeat analysis appear to identify little diversity within these molecular subtypes. Given the apparent expansion of these subtypes into new geographic areas and their ability to cause disease in immunocompetent individuals, differentiation of isolates belonging to these subtypes could be very important from a public health perspective. We used whole genome sequence typing (WGST) to perform fine-scale phylogenetic analysis on 20 C. gattii isolates, 18 of which are from the VGII molecular type largely responsible for the Pacific Northwest emergence. Analysis both including and excluding (289,586 SNPs and 56,845 SNPs, respectively) molecular types VGI and VGIII isolates resulted in phylogenetic reconstructions consistent, for the most part, with MLST analysis but with far greater resolution among isolates. The WGST analysis presented here resulted in identification of over 100 SNPs among eight VGIIc isolates as well as unique genotypes for each of the VGIIa, VGIIb and VGIIc isolates. Similar levels of genetic diversity were found within each of the molecular subtype isolates, despite the fact that the VGIIb clade is thought to have emerged much earlier. The analysis presented here is the first multi-genome WGST study to focus on the C. gattii molecular subtypes involved in the Pacific Northwest emergence and describes the tools that will further our understanding of this emerging pathogen.
authors.affiliation: Pathogen Genomics Division, Translational Genomics Research Institute, Flagstaff, Arizona, United States of America.
authors.forename: John D
authors.initials: JD
authors.lastname: Gillece
authors.forename: James M
authors.initials: JM
authors.lastname: Schupp
authors.forename: S Arunmozhi
authors.initials: SA
authors.lastname: Balajee
authors.forename: Julie
authors.initials: J
authors.lastname: Harris
authors.forename: Talima
authors.initials: T
authors.lastname: Pearson
authors.forename: Yongpan
authors.initials: Y
authors.lastname: Yan
authors.forename: Paul
authors.initials: P
authors.lastname: Keim
authors.forename: Emilio
authors.initials: E
authors.lastname: DeBess
authors.forename: Nicola
authors.initials: N
authors.lastname: Marsden-Haug
authors.forename: Ron
authors.initials: R
authors.lastname: Wohrle
authors.forename: David M
authors.initials: DM
authors.lastname: Engelthaler
authors.forename: Shawn R
authors.initials: SR
authors.lastname: Lockhart
mesh_terms: D044822:Biodiversity; D003453:Cryptococcosis / Q000382:microbiology*; D056285:Cryptococcus gattii / Q000235:genetics*; D014644:Genetic Variation; D016678:Genome; D016681:Genome, Fungal; D005838:Genotype; D005843:Geography; D010802:Phylogeny; D011014:Pneumonia / Q000382:microbiology*; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA; D013045:Species Specificity