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Title: Cryptococcus gattii in North American Pacific Northwest: Whole-population genome analysis provides insights into species evolution and dispersal
Authors: David M. Engelthaler
Nathan D. Hicks
John D. Gillece
Chandler C. Roe
James M. Schupp
Elizabeth M. Driebe
Felix Gilgado
Fabian Carriconde
Luciana Trilles
Carolina Firacative
Popchai Ngamskulrungroj
Elizabeth Castañeda
Marcia Dos Santos Lazera
Marcia S.C. Melhem
Åsa Pérez-Bercoff
Gavin Huttley
Tania C. Sorrell
Kerstin Voelz
Robin C. May
Matthew C. Fisher
George R. Thompson
Shawn R. Lockhart
Paul Keim
Wieland Meyer
Translational Genomics Research Institute
The University of Sydney
Institut Agronomique Néo-Calédonien (IAC)
Fundacao Oswaldo Cruz
Instituto Nacional de Salud
Mahidol University
Instituto Adolfo Lutz
Australian National University
University of Birmingham
Queen Elizabeth Hospital, University Hospital Birmingham NHS Foundation Trust
Imperial College London
University of California, Davis
Centers for Disease Control and Prevention
Northern Arizona University
Keywords: Immunology and Microbiology
Issue Date: 15-Jul-2014
Citation: mBio. Vol.5, No.4 (2014)
Abstract: © 2014 Engelthaler et al. 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.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.
ISSN: 21507511
Appears in Collections:Scopus 2011-2015

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