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Cryptococcus gattii in North American Pacific Northwest: whole-population genome analysis provides insights into species evolution and dispersal

Engelthaler, David M. and Hicks, Nathan D. and Gillece, John D. and Roe, Chandler C. and Schupp, James M. and Driebe, Elizabeth M. and Gilgado, Felix and Carriconde, Fabian and Trilles, Luciana and Firacative, Carolina and Ngamskulrungroj, Popchai and Castañeda, Elizabeth and Lazera, Marcia dos Santos and Melhem, Marcia S. C. and Pérez-Bercoff, Asa and Huttley, Gavin and Sorrell, Tania C. and Voelz, Kerstin and May, Robin C. and Fisher, Matthew C. and Thompson, George R. and Lockhart, Shawn R. and Keim, Paul and Meyer, Wieland (2014) Cryptococcus gattii in North American Pacific Northwest: whole-population genome analysis provides insights into species evolution and dispersal. mBio, 5 (4). pp. 1-18. ISSN 2150-7511

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Publisher’s or external URL: http://dx.doi.org/10.1128/mBio.01464-14


The emergence of distinct populations of Cryptococcus gattii in the temperate North American Pacific Northwest (PNW) was surprising, as this species was previously thought to be confined to tropical and semitropical regions. Beyond a new habitat niche, the dominant emergent population displayed increased virulence and caused primary pulmonary disease, as opposed to the predominantly neurologic disease seen previously elsewhere. Whole-genome sequencing was performed on 118 C. gattii isolates, including the PNW subtypes and the global diversity of molecular type VGII, to better ascertain the natural source and genomic adaptations leading to the emergence of infection in the PNW. Overall, the VGII population was highly diverse, demonstrating large numbers of mutational and recombinational events; however, the three dominant subtypes from the PNW were of low diversity and were completely clonal. Although strains of VGII were found on at least five continents, all genetic subpopulations were represented or were most closely related to strains from South America. The phylogenetic data are consistent with multiple dispersal events from South America to North America and elsewhere. Numerous gene content differences were identified between the emergent clones and other VGII lineages, including genes potentially related to habitat adaptation, virulence, and pathology. Evidence was also found for possible gene introgression from Cryptococcus neoformans var. grubii that is rarely seen in global C. gattii but that was present in all PNW populations. These findings provide greater understanding of C. gattii evolution in North America and support extensive evolution in, and dispersal from, South America. Importance: Cryptococcus gattii emerged in the temperate North American Pacific Northwest (PNW) in the late 1990s. Beyond a new environmental niche, these emergent populations displayed increased virulence and resulted in a different pattern of clinical disease. In particular, severe pulmonary infections predominated in contrast to presentation with neurologic disease as seen previously elsewhere. We employed population-level whole-genome sequencing and analysis to explore the genetic relationships and gene content of the PNW C. gattii populations. We provide evidence that the PNW strains originated from South America and identified numerous genes potentially related to habitat adaptation, virulence expression, and clinical presentation. Characterization of these genetic features may lead to improved diagnostics and therapies for such fungal infections. The data indicate that there were multiple recent introductions of C. gattii into the PNW. Public health vigilance is warranted for emergence in regions where C. gattii is not thought to be endemic.

Item Type: Article
ID number or DOI: 10.1128/mBio.01464-14
Keywords: alpha-l-rhamnosidase; ecological niche; genetic diversity; glycoside hydrolase; lung epithelial-cells; Molecular epidemiology; natural habitat; neoformans var. gattii; phylogenetic networks; vancouver-island
Subjects: Q Science > QR Microbiology
NAU Depositing Author Academic Status: Faculty/Staff
Department/Unit: Research Centers > Center for Microbial Genetics and Genomics
Date Deposited: 12 Oct 2015 16:21
URI: http://openknowledge.nau.edu/id/eprint/1057

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