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Emergence and pathogenicity of highly virulent Cryptococcus gattii genotypes in the northwest United States.

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Date
2010-04-22
Authors
Byrnes 3rd, EJ
Li, W
Lewit, Y
Ma, H
Voelz, K
Ren, P
Carter, DA
Chaturvedi, V
Bildfell, RJ
May, RC
Heitman, J
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(11 total)
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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 article
Subject
Animals
Cluster Analysis
Cryptococcosis
Cryptococcus gattii
Disease Outbreaks
Female
Genotype
Humans
Mice
Mitochondria
Molecular Epidemiology
Northwestern United States
Polymerase Chain Reaction
Permalink
https://hdl.handle.net/10161/4598
Published Version (Please cite this version)
10.1371/journal.ppat.1000850
Publication 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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Scholars@Duke

Heitman

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 E
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