title: Effects of zinc transporters on Cryptococcus gattii virulence.
abstract: Zinc is an essential nutrient for all living organisms because it is a co-factor of several important proteins. Furthermore, zinc may play an essential role in the infectiousness of microorganisms. Previously, we determined that functional zinc metabolism is associated with Cryptococcus gattii virulence. Here, we characterized the ZIP zinc transporters in this human pathogen. Transcriptional profiling revealed that zinc levels regulated the expression of the ZIP1, ZIP2 and ZIP3 genes, although only the C. gattii zinc transporter Zip1 was required for yeast growth under zinc-limiting conditions. To associate zinc uptake defects with virulence, the most studied cryptococcal virulence factors (i.e., capsule, melanin and growth at 37 °C) were assessed in ZIP mutant strains; however, no differences were detected in these classical virulence-associated traits among the mutant and WT strains. Interestingly, higher levels of reactive oxygen species were detected in the zip1Δ and in the zip1Δ zip2Δ double mutants. In line with these phenotypic alterations, the zip1Δ zip2Δ double mutant displayed attenuated virulence in a murine model of cryptococcosis. Together, these results indicate that adequate zinc uptake is necessary for cryptococcal fitness and virulence.
authors.affiliation: Centro de Biotecnologia.
authors.forename: Rafael de Oliveira
authors.initials: RO
authors.lastname: Schneider
authors.affiliation: Centro de Biotecnologia.
authors.forename: Camila
authors.initials: C
authors.lastname: Diehl
authors.affiliation: Centro de Biotecnologia.
authors.forename: Francine Melise
authors.initials: FM
authors.lastname: Dos Santos
authors.affiliation: Centro de Biotecnologia.
authors.forename: Alícia Corbellini
authors.initials: AC
authors.lastname: Piffer
authors.affiliation: Centro de Biotecnologia.
authors.forename: Ane Wichine Acosta
authors.initials: AWA
authors.lastname: Garcia
authors.affiliation: Centro de Biotecnologia.
authors.forename: Marcos Iuri Roos
authors.initials: MIR
authors.lastname: Kulmann
authors.affiliation: Centro de Biotecnologia.|Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, 43421, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Augusto
authors.initials: A
authors.lastname: Schrank
authors.affiliation: Centro de Biotecnologia.|Departamento de Biologia Molecular e 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.affiliation: Centro de Biotecnologia.|Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, 43421, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Marilene Henning
authors.initials: MH
authors.lastname: Vainstein
authors.affiliation: Centro de Biotecnologia.|Departamento de Biologia Molecular e Biotecnologia, Universidade Federal do Rio Grande do Sul, Av. Bento Gonçalves 9500, 43421, Caixa Postal 15005, Porto Alegre, RS 91501-970, Brazil.
authors.forename: Charley C
authors.initials: CC
authors.lastname: Staats
mesh_terms: D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003453:Cryptococcosis / Q000382:microbiology*; D056285:Cryptococcus gattii / Q000235:genetics* / Q000378:metabolism / Q000472:pathogenicity*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D009154:Mutation; D017382:Reactive Oxygen Species / Q000378:metabolism; D014158:Transcription, Genetic; D014774:Virulence / Q000235:genetics; D015032:Zinc / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D017382:Reactive Oxygen Species; C017800:zinc-binding protein; D015032:Zinc