Journal
FUNGAL GENETICS AND BIOLOGY
Volume 48, Issue 2, Pages 192-199Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.fgb.2010.07.011
Keywords
Nitrogen metabolism; Nitrogen Catabolite Repression; Cryptococcus neoformans
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Funding
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq, Brazil)
- Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES, Brazil)
- Fundacao de Amparo a Pesquisa no Estado do Rio de Janeiro (FAPERJ, Brazil)
- Financiadora de Estudos e Projetos (FINEP, Brazil)
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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 GAD genes. In an attempt to define the function of this transcriptional regulator in C. neoformans, we generated null mutants (gat1 Delta) of this gene. The gat 1 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. Gal 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. (C) 2010 Elsevier Inc. All rights reserved.
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