<named-content content-type="genus-species">Cryptococcus gattii</named-content> in North American Pacific Northwest: Whole-Population Genome Analysis Provides Insights into Species Evolution and Dispersal
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
Affiliations
David M. Engelthaler
Translational Genomics Research Institute, Flagstaff, Arizona, USA
Nathan D. Hicks
Translational Genomics Research Institute, Flagstaff, Arizona, USA
John D. Gillece
Translational Genomics Research Institute, Flagstaff, Arizona, USA
Chandler C. Roe
Translational Genomics Research Institute, Flagstaff, Arizona, USA
James M. Schupp
Translational Genomics Research Institute, Flagstaff, Arizona, USA
Elizabeth M. Driebe
Translational Genomics Research Institute, Flagstaff, Arizona, USA
Felix Gilgado
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Fabian Carriconde
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Luciana Trilles
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Carolina Firacative
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Popchai Ngamskulrungroj
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Elizabeth Castañeda
Microbiology Group, Instituto Nacional de Salud, Bogotá, Colombia
Marcia dos Santos Lazera
Laboratório de Micologia, Instituto de Pesquisa Clínica Evandro Chagas, FIOCRUZ, Rio de Janeiro, Brazil
Marcia S. C. Melhem
Public Health Reference Laboratory, Institute Adolfo Lutz, São Paulo, SP, Brazil
Åsa Pérez-Bercoff
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Gavin Huttley
John Curtin School of Medical Research, Australian National University, Canberra, Australia
Tania C. Sorrell
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
Kerstin Voelz
Institute of Microbiology and Infection and School of Biosciences, University of Birmingham, Birmingham, United Kingdom
Robin C. May
Institute of Microbiology and Infection and School of Biosciences, University of Birmingham, Birmingham, United Kingdom
Matthew C. Fisher
Department of Infectious Disease Epidemiology, Imperial College London, London, United Kingdom
George R. Thompson
University of California, Davis, Davis, California, USA
Shawn R. Lockhart
Centers for Disease Control and Prevention, Atlanta, Georgia, USA
Paul Keim
Translational Genomics Research Institute, Flagstaff, Arizona, USA
Wieland Meyer
Molecular Mycology Research Laboratory, Center for Infectious Diseases and Microbiology, Sydney Medical School, Westmead Hospital, Marie Bashir Institute for Infectious Diseases and Biosecurity, The University of Sydney, Westmead Millennium Institute, Sydney, Australia
ABSTRACT 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.