title: Transcriptional profile of Paracoccidioides spp. in response to itraconazole.
abstract: BACKGROUND
  Itraconazole is currently used to treat paracoccidioidomycosis. The mechanism of action of azoles has been elucidated in some fungi, although little is known regarding its mechanism of action in Paracoccidioides spp. The present work focused on identification of regulated transcripts using representational difference analysis of Paracoccidioides spp. yeast cells treated with itraconazole for 1 and 2 h.
  
  
  RESULTS
  Paracoccidioides Pb01 genes up-regulated by itraconazole included genes involved in cellular transport, metabolism/energy, transcription, cell rescue, defense and virulence. ERG11, ERG6, ERG3, ERG5 and ERG25 were up-regulated at multiple time points. In vivo infection experiments in mice corroborated the in vitro results. Ergosterol levels and distribution were evaluated in Paracoccidioides Pb18 yeast cells, and the results demonstrate that both factors were changed in the fungus treated with itraconazole.
  
  
  CONCLUSIONS
  To our knowledge, this is the first transcriptional analysis of Paracoccidioides spp. exposed to a triazole drug. Here acetyl seems to be intensively produced from different metabolic pathways to produce ergosterol by the action of ergosterol synthesis related enzymes, which were also affected in other fungi. Among the genes affected, we identified genes in common with other fungi, as well as genes unique to Paracoccidioides Pb01. Those genes could be considered target to new drugs. Voltage-gated Ca2+ alpha subunit (CAV), Tetracycline resistance protein (TETA) and Hemolisyn-iii channel protein (HLYiii) were found only here and a probably involvement with resistance to itraconazole could be investigated in the future. However our findings do not permit inference to current clinical practice.
authors.forename: Benedito Rodrigues
authors.initials: BR
authors.lastname: da Silva Neto
authors.forename: Patrícia Fernanda Zambuzzi
authors.initials: PF
authors.lastname: Carvalho
authors.forename: Alexandre Melo
authors.initials: AM
authors.lastname: Bailão
authors.forename: Wellington Santos
authors.initials: WS
authors.lastname: Martins
authors.forename: Célia Maria de Almeida
authors.initials: CM
authors.lastname: Soares
authors.affiliation: Departamento de Bioquímica e Biologia Molecular, Laboratório de Biologia Molecular, Instituto de Ciências Biológicas, ICBII, Campus II, Universidade Federal de Goiás, C,P, 131, 74001-970 Goiânia, GO, Brazil. maristelaufg@gmail.com.
authors.forename: Maristela
authors.initials: M
authors.lastname: Pereira
mesh_terms: D000220:Adaptation, Biological / Q000187:drug effects / Q000235:genetics; D000935:Antifungal Agents / Q000494:pharmacology*; D001692:Biological Transport; D019295:Computational Biology; D004875:Ergosterol / Q000378:metabolism; D020869:Gene Expression Profiling; D015966:Gene Expression Regulation, Fungal / Q000187:drug effects*; D005800:Genes, Fungal; D017964:Itraconazole / Q000494:pharmacology*; D008954:Models, Biological; D010228:Paracoccidioides / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism; D014158:Transcription, Genetic; D059467:Transcriptome
chemical_list: D000935:Antifungal Agents; D017964:Itraconazole; D004875:Ergosterol