Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States.
Abstract
Cryptococcus gattii causes life-threatening disease in otherwise healthy hosts and
to a lesser extent in immunocompromised hosts. The highest incidence for this disease
is on Vancouver Island, Canada, where an outbreak is expanding into neighboring regions
including mainland British Columbia and the United States. This outbreak is caused
predominantly by C. gattii molecular type VGII, specifically VGIIa/major. In addition,
a novel genotype, VGIIc, has emerged in Oregon and is now a major source of illness
in the region. Through molecular epidemiology and population analysis of MLST and
VNTR markers, we show that the VGIIc group is clonal and hypothesize it arose recently.
The VGIIa/IIc outbreak lineages are sexually fertile and studies support ongoing recombination
in the global VGII population. This illustrates two hallmarks of emerging outbreaks:
high clonality and the emergence of novel genotypes via recombination. In macrophage
and murine infections, the novel VGIIc genotype and VGIIa/major isolates from the
United States are highly virulent compared to similar non-outbreak VGIIa/major-related
isolates. Combined MLST-VNTR analysis distinguishes clonal expansion of the VGIIa/major
outbreak genotype from related but distinguishable less-virulent genotypes isolated
from other geographic regions. Our evidence documents emerging hypervirulent genotypes
in the United States that may expand further and provides insight into the possible
molecular and geographic origins of the outbreak.
Type
Journal articleSubject
AnimalsCluster Analysis
Cryptococcosis
Cryptococcus gattii
Disease Outbreaks
Female
Genotype
Humans
Mice
Mitochondria
Molecular Epidemiology
Northwestern United States
Polymerase Chain Reaction
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https://hdl.handle.net/10161/4598Published Version (Please cite this version)
10.1371/journal.ppat.1000850Publication Info
Byrnes 3rd, EJ; Li, W; Lewit, Y; Ma, H; Voelz, K; Ren, P; ... Heitman, J (2010). Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the
northwest United States. PLoS Pathog, 6(4). pp. e1000850. 10.1371/journal.ppat.1000850. Retrieved from https://hdl.handle.net/10161/4598.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Show full item recordScholars@Duke
Joseph Heitman
Chair, Department of Molecular Genetics and Microbiology
Joseph Heitman was an undergraduate at the University of Chicago (1980-1984), graduating
from the BS-MS program with dual degrees in chemistry and biochemistry with general
and special honors. He then matriculated as an MD-PhD student at Cornell and Rockefeller
Universities and worked with Peter Model and Norton Zinder on how restriction enzymes
recognize specific DNA sequences and how bacteria respond to and repair DNA breaks
and nicks. Dr. Heitman moved as an EMBO long-term fellow to the Bi

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