The GATA-type transcriptional activator Gat1 regulates nitrogen uptake and metabolism in the human pathogen Cryptococcus neoformans
| Autor: | Augusto Schrank, Elisa de Saldanha Simon, Suely Lopes Gomes, Marcio L. Rodrigues, Luna S. Joffe, Jéssica Rodrigues, Leonardo Nimrichter, Livia Kmetzsch, Fernanda L. Fonseca, Charley Christian Staats, Débora L. Oliveira, Rogério F. Lourenço, Marilene Henning Vainstein |
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| Rok vydání: | 2011 |
| Předmět: |
Nitrogen
Mutant GATA Transcription Factors Regulon Microbiology Aspergillus nidulans Fungal Proteins NITROGÊNIO Mice Gene Expression Regulation Fungal Candida albicans Genetics Transcriptional regulation Animals Gene Cryptococcus neoformans Zinc finger Mice Inbred BALB C Sequence Homology Amino Acid Virulence biology Gene Expression Profiling Macrophages Zinc Fingers Cryptococcosis Microarray Analysis biology.organism_classification Survival Analysis Disease Models Animal Biochemistry Cell wall organization Trans-Activators Female Gene Deletion |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP |
| ISSN: | 1087-1845 |
| DOI: | 10.1016/j.fgb.2010.07.011 |
| Popis: | Nitrogen uptake and metabolism are essential to microbial growth. Gat1 belongs to a conserved family of zinc finger containing transcriptional regulators known as GATA-factors. These factors activate the transcription of Nitrogen Catabolite Repression (NCR) sensitive genes when preferred nitrogen sources are absent or limiting. Cryptococcus neoformans GAT1 is an ortholog to the Aspergillus nidulans AreA and Candida albicans GAT1 genes. In an attempt to define the function of this transcriptional regulator in C. neoformans, we generated null mutants (gat1Δ) of this gene. The gat1 mutant exhibited impaired growth on all amino acids tested as sole nitrogen sources, with the exception of arginine and proline. Furthermore, the gat1 mutant did not display resistance to rapamycin, an immunosuppressant drug that transiently mimics a low-quality nitrogen source. Gat1 is not required for C. neoformans survival during macrophage infection or for virulence in a mouse model of cryptococcosis. Microarray analysis allowed the identification of target genes that are regulated by Gat1 in the presence of proline, a poor and non-repressing nitrogen source. Genes involved in ergosterol biosynthesis, iron uptake, cell wall organization and capsule biosynthesis, in addition to NCR-sensitive genes, are Gat1-regulated in C. neoformans. |
| Databáze: | OpenAIRE |
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