title: The GATA-type transcriptional activator Gat1 regulates nitrogen uptake and metabolism in the human pathogen Cryptococcus neoformans.
abstract: 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.
authors.affiliation: Centro de Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, 43421, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Lívia
authors.initials: L
authors.lastname: Kmetzsch
authors.forename: Charley Christian
authors.initials: CC
authors.lastname: Staats
authors.forename: Elisa
authors.initials: E
authors.lastname: Simon
authors.forename: Fernanda L
authors.initials: FL
authors.lastname: Fonseca
authors.forename: Débora L
authors.initials: DL
authors.lastname: Oliveira
authors.forename: Luna S
authors.initials: LS
authors.lastname: Joffe
authors.forename: Jéssica
authors.initials: J
authors.lastname: Rodrigues
authors.forename: Rogério F
authors.initials: RF
authors.lastname: Lourenço
authors.forename: Suely L
authors.initials: SL
authors.lastname: Gomes
authors.forename: Leonardo
authors.initials: L
authors.lastname: Nimrichter
authors.forename: Marcio L
authors.initials: ML
authors.lastname: Rodrigues
authors.forename: Augusto
authors.initials: A
authors.lastname: Schrank
authors.forename: Marilene Henning
authors.initials: MH
authors.lastname: Vainstein
mesh_terms: D000818:Animals; D001233:Aspergillus nidulans / Q000235:genetics; D002176:Candida albicans / Q000235:genetics; D003453:Cryptococcosis / Q000382:microbiology; D003455:Cryptococcus neoformans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism / Q000502:physiology*; D004195:Disease Models, Animal; D005260:Female; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D050980:GATA Transcription Factors / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal; D008264:Macrophages / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D046228:Microarray Analysis; D009584:Nitrogen / Q000378:metabolism*; D018085:Regulon; D017386:Sequence Homology, Amino Acid; D016019:Survival Analysis; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D014774:Virulence; D016335:Zinc Fingers
chemical_list: D005656:Fungal Proteins; C561705:GAT1 protein, Cryptococcus neoformans; D050980:GATA Transcription Factors; D015534:Trans-Activators; D009584:Nitrogen