MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors.
The emerging pathogen Cryptococcus gattii causes life-threatening disease in immunocompetent and immunocompromised hosts. Of the four major molecular types (VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in otherwise healthy individuals, prompting a need to investigate...
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Format: | Article |
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Public Library of Science (PLoS)
2016-08-01
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Series: | PLoS Neglected Tropical Diseases |
Online Access: | http://europepmc.org/articles/PMC4975453?pdf=render |
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author | Carolina Firacative Chandler C Roe Richard Malik Kennio Ferreira-Paim Patricia Escandón Jane E Sykes Laura Rocío Castañón-Olivares Cudberto Contreras-Peres Blanca Samayoa Tania C Sorrell Elizabeth Castañeda Shawn R Lockhart David M Engelthaler Wieland Meyer |
author_facet | Carolina Firacative Chandler C Roe Richard Malik Kennio Ferreira-Paim Patricia Escandón Jane E Sykes Laura Rocío Castañón-Olivares Cudberto Contreras-Peres Blanca Samayoa Tania C Sorrell Elizabeth Castañeda Shawn R Lockhart David M Engelthaler Wieland Meyer |
author_sort | Carolina Firacative |
collection | DOAJ |
description | The emerging pathogen Cryptococcus gattii causes life-threatening disease in immunocompetent and immunocompromised hosts. Of the four major molecular types (VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in otherwise healthy individuals, prompting a need to investigate its population genetic structure to understand if there are potential genotype-dependent characteristics in its epidemiology, environmental niche(s), host range and clinical features of disease. Multilocus sequence typing (MLST) of 122 clinical, environmental and veterinary C. gattii VGIII isolates from Australia, Colombia, Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela, and whole genome sequencing (WGS) of 60 isolates representing all established MLST types identified four divergent sub-populations. The majority of the isolates belong to two main clades, corresponding either to serotype B or C, indicating an ongoing species evolution. Both major clades included clinical, environmental and veterinary isolates. The C. gattii VGIII population was genetically highly diverse, with minor differences between countries, isolation source, serotype and mating type. Little to no recombination was found between the two major groups, serotype B and C, at the whole and mitochondrial genome level. C. gattii VGIII is widespread in the Americas, with sporadic cases occurring elsewhere, WGS revealed Mexico and USA as a likely origin of the serotype B VGIII population and Colombia as a possible origin of the serotype C VGIII population. Serotype B isolates are more virulent than serotype C isolates in a murine model of infection, causing predominantly pulmonary cryptococcosis. No specific link between genotype and virulence was observed. Antifungal susceptibility testing against six antifungal drugs revealed that serotype B isolates are more susceptible to azoles than serotype C isolates, highlighting the importance of strain typing to guide effective treatment to improve the disease outcome. |
first_indexed | 2024-12-19T18:59:29Z |
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institution | Directory Open Access Journal |
issn | 1935-2727 1935-2735 |
language | English |
last_indexed | 2024-12-19T18:59:29Z |
publishDate | 2016-08-01 |
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series | PLoS Neglected Tropical Diseases |
spelling | doaj.art-894276a2a172407f8fb682c7b6b55fc32022-12-21T20:09:35ZengPublic Library of Science (PLoS)PLoS Neglected Tropical Diseases1935-27271935-27352016-08-01108e000486110.1371/journal.pntd.0004861MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors.Carolina FiracativeChandler C RoeRichard MalikKennio Ferreira-PaimPatricia EscandónJane E SykesLaura Rocío Castañón-OlivaresCudberto Contreras-PeresBlanca SamayoaTania C SorrellElizabeth CastañedaShawn R LockhartDavid M EngelthalerWieland MeyerThe emerging pathogen Cryptococcus gattii causes life-threatening disease in immunocompetent and immunocompromised hosts. Of the four major molecular types (VGI-VGIV), the molecular type VGIII has recently emerged as cause of disease in otherwise healthy individuals, prompting a need to investigate its population genetic structure to understand if there are potential genotype-dependent characteristics in its epidemiology, environmental niche(s), host range and clinical features of disease. Multilocus sequence typing (MLST) of 122 clinical, environmental and veterinary C. gattii VGIII isolates from Australia, Colombia, Guatemala, Mexico, New Zealand, Paraguay, USA and Venezuela, and whole genome sequencing (WGS) of 60 isolates representing all established MLST types identified four divergent sub-populations. The majority of the isolates belong to two main clades, corresponding either to serotype B or C, indicating an ongoing species evolution. Both major clades included clinical, environmental and veterinary isolates. The C. gattii VGIII population was genetically highly diverse, with minor differences between countries, isolation source, serotype and mating type. Little to no recombination was found between the two major groups, serotype B and C, at the whole and mitochondrial genome level. C. gattii VGIII is widespread in the Americas, with sporadic cases occurring elsewhere, WGS revealed Mexico and USA as a likely origin of the serotype B VGIII population and Colombia as a possible origin of the serotype C VGIII population. Serotype B isolates are more virulent than serotype C isolates in a murine model of infection, causing predominantly pulmonary cryptococcosis. No specific link between genotype and virulence was observed. Antifungal susceptibility testing against six antifungal drugs revealed that serotype B isolates are more susceptible to azoles than serotype C isolates, highlighting the importance of strain typing to guide effective treatment to improve the disease outcome.http://europepmc.org/articles/PMC4975453?pdf=render |
spellingShingle | Carolina Firacative Chandler C Roe Richard Malik Kennio Ferreira-Paim Patricia Escandón Jane E Sykes Laura Rocío Castañón-Olivares Cudberto Contreras-Peres Blanca Samayoa Tania C Sorrell Elizabeth Castañeda Shawn R Lockhart David M Engelthaler Wieland Meyer MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. PLoS Neglected Tropical Diseases |
title | MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. |
title_full | MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. |
title_fullStr | MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. |
title_full_unstemmed | MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. |
title_short | MLST and Whole-Genome-Based Population Analysis of Cryptococcus gattii VGIII Links Clinical, Veterinary and Environmental Strains, and Reveals Divergent Serotype Specific Sub-populations and Distant Ancestors. |
title_sort | mlst and whole genome based population analysis of cryptococcus gattii vgiii links clinical veterinary and environmental strains and reveals divergent serotype specific sub populations and distant ancestors |
url | http://europepmc.org/articles/PMC4975453?pdf=render |
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