Functional and genetic characterization of calmodulin from the dimorphic and pathogenic fungus Paracoccidioides brasiliensis.
Calmodulin (CaM) modulates intracellular calcium signalling and acts on several metabolic pathways and gene expression regulation in many eukaryotic organisms including human fungal pathogens, such as Candida albicans and Histoplasma capsulatum. The temperature-dependent dimorphic fungus Paracoccidioides brasiliensis is the aetiological agent of paracoccidioidomycosis (PCM). The mycelium (M) to yeast (Y) transition has been shown to be essential for establishment of the infection, although the precise molecular mechanisms of dimorphism in P. brasiliensis are still unknown. In this work, several inhibitory drugs of the Ca(2+)/calmodulin signalling pathway were tested to verify the role of this pathway in the cellular differentiation process of P. brasiliensis. EGTA and the drugs calmidazolium (R24571), trifluoperazine (TFP), and W7 were able to inhibit the M-Y transition. We have cloned and characterized the calmodulin gene from P. brasiliensis, which comprises 924 nucleotides and five introns that are in a conserved position among calmodulin genes.
de Carvalho
Maria José A
MJ
Lab. de Biologia Molecular, IB, Campus Universitá rio Darcy Ribeiro, Universidade de Brasília, 70910-900 Brasília-DF, Brazil.
Amorim Jesuino
Rosália S
RS
Daher
Bruno S
BS
Silva-Pereira
Ildinete
I
de Freitas
Sonia M
SM
Soares
Célia M A
CM
Felipe
M Sueli S
MS
D000595:Amino Acid Sequence; D001483:Base Sequence; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics* / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D004271:DNA, Fungal / Q000737:chemistry; D004533:Egtazic Acid / Q000494:pharmacology; D005656:Fungal Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D018628:Gene Dosage; D005800:Genes, Fungal / Q000502:physiology; D016681:Genome, Fungal; D007093:Imidazoles / Q000494:pharmacology; D007438:Introns; D008969:Molecular Sequence Data; D025282:Mycelium; D010228:Paracoccidioides / Q000166:cytology* / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017385:Sequence Homology; D014268:Trifluoperazine / Q000494:pharmacology; D015003:Yeasts
D002147:Calmodulin; D002614:Chelating Agents; D004271:DNA, Fungal; D005656:Fungal Proteins; D007093:Imidazoles; D014268:Trifluoperazine; C031938:calmidazolium; D004533:Egtazic Acid