Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii.
Zinc homeostasis is essential for fungal growth, as this metal is a critical structural component of several proteins, including transcription factors. The fungal pathogen Cryptococcus gattii obtains zinc from the stringent zinc-limiting milieu of the host during the infection process. To characteri...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3423376?pdf=render |
| _version_ | 1818096158380130304 |
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| author | Rafael de Oliveira Schneider Natully de Souza Süffert Fogaça Lívia Kmetzsch Augusto Schrank Marilene Henning Vainstein Charley Christian Staats |
| author_facet | Rafael de Oliveira Schneider Natully de Souza Süffert Fogaça Lívia Kmetzsch Augusto Schrank Marilene Henning Vainstein Charley Christian Staats |
| author_sort | Rafael de Oliveira Schneider |
| collection | DOAJ |
| description | Zinc homeostasis is essential for fungal growth, as this metal is a critical structural component of several proteins, including transcription factors. The fungal pathogen Cryptococcus gattii obtains zinc from the stringent zinc-limiting milieu of the host during the infection process. To characterize the zinc metabolism in C. gattii and its relationship to fungal virulence, the zinc finger protein Zap1 was functionally characterized. The C. gattii ZAP1 gene is an ortholog of the master regulatory genes zafA and ZAP1 that are found in Aspergillus fumigatus and Saccharomyces cerevisiae, respectively. There is some evidence to support an association between Zap1 and zinc metabolism in C. gattii: (i) ZAP1 expression is highly induced during zinc deprivation, (ii) ZAP1 knockouts demonstrate impaired growth in zinc-limiting conditions, (iii) Zap1 regulates the expression of ZIP zinc transporters and distinct zinc-binding proteins and (iv) Zap1 regulates the labile pool of intracellular zinc. In addition, the deletion of ZAP1 reduces C. gattii virulence in a murine model of cryptococcosis infection. Based on these observations, we postulate that proper zinc metabolism plays a crucial role in cryptococcal virulence. |
| first_indexed | 2024-12-10T23:00:10Z |
| format | Article |
| id | doaj.art-d58441484a00468c8bbd05c420ac9be6 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-10T23:00:10Z |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
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| series | PLoS ONE |
| spelling | doaj.art-d58441484a00468c8bbd05c420ac9be62022-12-22T01:30:09ZengPublic Library of Science (PLoS)PLoS ONE1932-62032012-01-0178e4377310.1371/journal.pone.0043773Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii.Rafael de Oliveira SchneiderNatully de Souza Süffert FogaçaLívia KmetzschAugusto SchrankMarilene Henning VainsteinCharley Christian StaatsZinc homeostasis is essential for fungal growth, as this metal is a critical structural component of several proteins, including transcription factors. The fungal pathogen Cryptococcus gattii obtains zinc from the stringent zinc-limiting milieu of the host during the infection process. To characterize the zinc metabolism in C. gattii and its relationship to fungal virulence, the zinc finger protein Zap1 was functionally characterized. The C. gattii ZAP1 gene is an ortholog of the master regulatory genes zafA and ZAP1 that are found in Aspergillus fumigatus and Saccharomyces cerevisiae, respectively. There is some evidence to support an association between Zap1 and zinc metabolism in C. gattii: (i) ZAP1 expression is highly induced during zinc deprivation, (ii) ZAP1 knockouts demonstrate impaired growth in zinc-limiting conditions, (iii) Zap1 regulates the expression of ZIP zinc transporters and distinct zinc-binding proteins and (iv) Zap1 regulates the labile pool of intracellular zinc. In addition, the deletion of ZAP1 reduces C. gattii virulence in a murine model of cryptococcosis infection. Based on these observations, we postulate that proper zinc metabolism plays a crucial role in cryptococcal virulence.http://europepmc.org/articles/PMC3423376?pdf=render |
| spellingShingle | Rafael de Oliveira Schneider Natully de Souza Süffert Fogaça Lívia Kmetzsch Augusto Schrank Marilene Henning Vainstein Charley Christian Staats Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. PLoS ONE |
| title | Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. |
| title_full | Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. |
| title_fullStr | Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. |
| title_full_unstemmed | Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. |
| title_short | Zap1 regulates zinc homeostasis and modulates virulence in Cryptococcus gattii. |
| title_sort | zap1 regulates zinc homeostasis and modulates virulence in cryptococcus gattii |
| url | http://europepmc.org/articles/PMC3423376?pdf=render |
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