Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts

D'Souza, C.A., Kronstad, J.W., Taylor, G., Warrne, R., Yuen, M., Hu, G., Jung, W.H., Sham, A., Kidd, S.E., Tangen, K., Lee, N., Zeilmaker, T., Sawkins, J., McVicker, G., Shah, S., Gnerre, S., Griggs, A., Zeng, Q., Bartlett, K., Li, W., Wang, X., Heitman, J., Stajich, J.E., Fraser, J.A., Meyer, W., Carter, D., Schein, J., Krzywinski, M., Kwon-Chung, K.J., Varma, A., Wang, J., Brunham, R., Fyfe, M., Ouellette, B.F.F., Siddiqui, A., Marra, M., Jones, S., Holt, R., Birren, B.W., Galagan, J.E. and Cuomo, C.A. (2011) Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts. mBio, 2 1: e00342-1-e00342-10. doi:10.1128/mBio.00342-10

Author D'Souza, C.A.
Kronstad, J.W.
Taylor, G.
Warrne, R.
Yuen, M.
Hu, G.
Jung, W.H.
Sham, A.
Kidd, S.E.
Tangen, K.
Lee, N.
Zeilmaker, T.
Sawkins, J.
McVicker, G.
Shah, S.
Gnerre, S.
Griggs, A.
Zeng, Q.
Bartlett, K.
Li, W.
Wang, X.
Heitman, J.
Stajich, J.E.
Fraser, J.A.
Meyer, W.
Carter, D.
Schein, J.
Krzywinski, M.
Kwon-Chung, K.J.
Varma, A.
Wang, J.
Brunham, R.
Fyfe, M.
Ouellette, B.F.F.
Siddiqui, A.
Marra, M.
Jones, S.
Holt, R.
Birren, B.W.
Galagan, J.E.
Cuomo, C.A.
Title Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts
Formatted title
Genome Variation in Cryptococcus gattii, an Emerging Pathogen of Immunocompetent Hosts
Journal name mBio   Check publisher's open access policy
ISSN 2161-2129
Publication date 2011-02-08
Year available 2011
Sub-type Article (original research)
DOI 10.1128/mBio.00342-10
Open Access Status DOI
Volume 2
Issue 1
Start page e00342-1
End page e00342-10
Total pages 11
Editor Arturo Casadevall
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2012
Language eng
Formatted abstract
Cryptococcus gattii recently emerged as the causative agent of cryptococcosis in healthy individuals in western North America, despite previous characterization of the fungus as a pathogen in tropical or subtropical regions. As a foundation to study the genetics of virulence in this pathogen, we sequenced the genomes of a strain (WM276) representing the predominant global molecular type (VGI) and a clinical strain (R265) of the major genotype (VGIIa) causing disease in North America. We compared these C. gattii genomes with each other and with the genomes of representative strains of the two varieties of Cryptococcus neoformans that generally cause disease in immunocompromised people. Our comparisons included chromosome alignments, analysis of gene content and gene family evolution, and comparative genome hybridization (CGH). These studies revealed that the genomes of the two representative C. gattii strains (genotypes VGI and VGIIa) are colinear for the majority of chromosomes, with some minor rearrangements. However, multiortholog phylogenetic analysis and an evaluation of gene/sequence conservation support the existence of speciation within the C. gattii complex. More extensive chromosome rearrangements were observed upon comparison of the C. gattii and the C. neoformans genomes. Finally, CGH revealed considerable variation in clinical and environmental isolates as well as changes in chromosome copy numbers in C. gattii isolates displaying fluconazole heteroresistance.

IMPORTANCE Isolates of Cryptococcus gattii are currently causing an outbreak of cryptococcosis in western North America, and most of the cases occurred in the absence of coinfection with HIV. This pattern is therefore in stark contrast to the current global burden of one million annual cases of cryptococcosis, caused by the related species Cryptococcus neoformans, in the HIV/AIDS population. The genome sequences of two outbreak-associated major genotypes of C. gattii reported here provide insights into genome variation within and between cryptococcal species. These sequences also provide a resource to further evaluate the epidemiology of cryptococcal disease and to evaluate the role of pathogen genes in the differential interactions of C. gattii and C. neoformans with immunocompromised and immunocompetent hosts.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Chemistry and Molecular Biosciences
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Citation counts: TR Web of Science Citation Count  Cited 60 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 48 times in Scopus Article | Citations
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Created: Wed, 14 Mar 2012, 10:26:34 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences