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Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii
The pathogenic yeast Cryptococcus gattii, which is causing an outbreak in the Pacific Northwest region of North America, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike Cryptococcus neoformans, which commonly infects immunocompromised patients. In...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Genetics Society of America
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583459/ https://www.ncbi.nlm.nih.gov/pubmed/23450261 http://dx.doi.org/10.1534/g3.112.004242 |
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author | Chen, Ying-Lien Lehman, Virginia N. Lewit, Yonathan Averette, Anna F. Heitman, Joseph |
author_facet | Chen, Ying-Lien Lehman, Virginia N. Lewit, Yonathan Averette, Anna F. Heitman, Joseph |
author_sort | Chen, Ying-Lien |
collection | PubMed |
description | The pathogenic yeast Cryptococcus gattii, which is causing an outbreak in the Pacific Northwest region of North America, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike Cryptococcus neoformans, which commonly infects immunocompromised patients. In addition to a greater predilection for C. gattii to infect healthy hosts, the C. gattii genome sequence project revealed extensive chromosomal rearrangements compared with C. neoformans, showing genomic differences between the two Cryptococcus species. We investigated the roles of C. gattii calcineurin in three molecular types: VGIIa (R265), VGIIb (R272), and VGI (WM276). We found that calcineurin exhibits a differential requirement for growth on solid medium at 37°, as calcineurin mutants generated from R265 were more thermotolerant than mutants from R272 and WM276. We demonstrated that tolerance to calcineurin inhibitors (FK506, CsA) at 37° is linked with the VGIIa molecular type. The calcineurin mutants from the R272 background showed the most extensive growth and morphological defects (multivesicle and larger ring-like cells), as well as increased fluconazole susceptibility. Our cellular architecture examination showed that C. gattii and C. neoformans calcineurin mutants exhibit plasma membrane disruptions. Calcineurin in the C. gattii VGII molecular type plays a greater role in controlling cation homeostasis compared with that in C. gattii VGI and C. neoformans H99. Importantly, we demonstrate that C. gattii calcineurin is essential for virulence in a murine inhalation model, supporting C. gattii calcineurin as an attractive antifungal drug target. |
format | Online Article Text |
id | pubmed-3583459 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Genetics Society of America |
record_format | MEDLINE/PubMed |
spelling | pubmed-35834592013-03-01 Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii Chen, Ying-Lien Lehman, Virginia N. Lewit, Yonathan Averette, Anna F. Heitman, Joseph G3 (Bethesda) Investigations The pathogenic yeast Cryptococcus gattii, which is causing an outbreak in the Pacific Northwest region of North America, causes life-threatening pulmonary infections and meningoencephalitis in healthy individuals, unlike Cryptococcus neoformans, which commonly infects immunocompromised patients. In addition to a greater predilection for C. gattii to infect healthy hosts, the C. gattii genome sequence project revealed extensive chromosomal rearrangements compared with C. neoformans, showing genomic differences between the two Cryptococcus species. We investigated the roles of C. gattii calcineurin in three molecular types: VGIIa (R265), VGIIb (R272), and VGI (WM276). We found that calcineurin exhibits a differential requirement for growth on solid medium at 37°, as calcineurin mutants generated from R265 were more thermotolerant than mutants from R272 and WM276. We demonstrated that tolerance to calcineurin inhibitors (FK506, CsA) at 37° is linked with the VGIIa molecular type. The calcineurin mutants from the R272 background showed the most extensive growth and morphological defects (multivesicle and larger ring-like cells), as well as increased fluconazole susceptibility. Our cellular architecture examination showed that C. gattii and C. neoformans calcineurin mutants exhibit plasma membrane disruptions. Calcineurin in the C. gattii VGII molecular type plays a greater role in controlling cation homeostasis compared with that in C. gattii VGI and C. neoformans H99. Importantly, we demonstrate that C. gattii calcineurin is essential for virulence in a murine inhalation model, supporting C. gattii calcineurin as an attractive antifungal drug target. Genetics Society of America 2013-03-01 /pmc/articles/PMC3583459/ /pubmed/23450261 http://dx.doi.org/10.1534/g3.112.004242 Text en Copyright © 2013 Chen et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution Unported License (http://creativecommons.org/licenses/by/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Investigations Chen, Ying-Lien Lehman, Virginia N. Lewit, Yonathan Averette, Anna F. Heitman, Joseph Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii |
title | Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii |
title_full | Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii |
title_fullStr | Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii |
title_full_unstemmed | Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii |
title_short | Calcineurin Governs Thermotolerance and Virulence of Cryptococcus gattii |
title_sort | calcineurin governs thermotolerance and virulence of cryptococcus gattii |
topic | Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3583459/ https://www.ncbi.nlm.nih.gov/pubmed/23450261 http://dx.doi.org/10.1534/g3.112.004242 |
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