Evidence for the role of calcineurin in morphogenesis and calcium homeostasis during mycelium-to-yeast dimorphism of Paracoccidioides brasiliensis

dc.contributorUniversidade Estadual Paulista (UNESP)
dc.creatorCampos, Claudia B. L.
dc.creatorDi Benedette, Joao Paulo T.
dc.creatorMorais, Flavia V.
dc.creatorOvalle, Rafael
dc.creatorNobrega, Marina P.
dc.date2014-05-27T11:23:40Z
dc.date2016-10-25T18:26:03Z
dc.date2014-05-27T11:23:40Z
dc.date2016-10-25T18:26:03Z
dc.date2008-10-01
dc.date.accessioned2017-04-06T01:32:35Z
dc.date.available2017-04-06T01:32:35Z
dc.identifierEukaryotic Cell, v. 7, n. 10, p. 1856-1864, 2008.
dc.identifier1535-9778
dc.identifierhttp://hdl.handle.net/11449/70595
dc.identifierhttp://acervodigital.unesp.br/handle/11449/70595
dc.identifier10.1128/EC.00110-08
dc.identifier2-s2.0-54249101880.pdf
dc.identifier2-s2.0-54249101880
dc.identifierhttp://dx.doi.org/10.1128/EC.00110-08
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/891677
dc.descriptionParacoccidioides brasiliensis is a dimorphic fungus that causes paracoccidioidomycosis, the most prevalent human deep mycosis in Latin America. The dimorphic transition from mycelium to yeast (M-Y) is triggered by a temperature shift from 25°C to 37°C and is critical for pathogenicity. Intracellular Ca 2+ levels increased in hyphae immediately after temperature-induced dimorphism. The chelation of Ca 2+ with extracellular (EGTA) or intracellular (BAPTA) calcium chelators inhibited temperature-induced dimorphism, whereas the addition of extracellular Ca 2+ accelerated dimorphism. The calcineurin inhibitor cyclosporine A (CsA), but not tacrolimus (FK506), effectively decreased cell growth, halted the M-Y transition that is associated with virulence, and caused aberrant growth morphologies for all forms of P. brasiliensis. The difference between CsA and FK506 was ascribed by the higher levels of cyclophilins contrasted to FKBPs, the intracellular drug targets required for calcineurin suppression. Chronic exposure to CsA abolished intracellular Ca 2+ homeostasis and decreased mRNA transcription of the CCH1 gene for the plasma membrane Ca 2+ channel in yeast-form cells. CsA had no detectable effect on multidrug resistance efflux pumps, while the effect of FK506 on rhodamine excretion was not correlated with the transition to yeast form. In this study, we present evidence that Ca 2+/calmodulin-dependent phosphatase calcineurin controls hyphal and yeast morphology, M-Y dimorphism, growth, and Ca 2+ homeostasis in P. brasiliensis and that CsA is an effective chemical block for thermodimorphism in this organism. The effects of calcineurin inhibitors on P. brasiliensis reinforce the therapeutic potential of these drugs in a combinatory approach with antifungal drugs to treat endemic paracoccidioidomycosis. Copyright © 2008, American Society for Microbiology. All Rights Reserved.
dc.languageeng
dc.relationEukaryotic Cell
dc.rightsinfo:eu-repo/semantics/closedAccess
dc.subjectcalcineurin
dc.subjectcalcium
dc.subjectcyclosporin
dc.subjectenzyme inhibitor
dc.subjectfungal protein
dc.subjecttacrolimus
dc.subjectdrug effect
dc.subjectenzymology
dc.subjectgene expression regulation
dc.subjectgenetics
dc.subjectgrowth, development and aging
dc.subjecthomeostasis
dc.subjecthuman
dc.subjectmetabolism
dc.subjectmicrobiology
dc.subjectmorphogenesis
dc.subjectmycelium
dc.subjectParacoccidioides
dc.subjectSouth American blastomycosis
dc.subjecttemperature
dc.subjectCalcineurin
dc.subjectCalcium
dc.subjectCyclosporine
dc.subjectEnzyme Inhibitors
dc.subjectFungal Proteins
dc.subjectGene Expression Regulation, Fungal
dc.subjectHomeostasis
dc.subjectHumans
dc.subjectMorphogenesis
dc.subjectMycelium
dc.subjectParacoccidioidomycosis
dc.subjectTacrolimus
dc.subjectTemperature
dc.subjectFungi
dc.subjectParacoccidioides brasiliensis
dc.titleEvidence for the role of calcineurin in morphogenesis and calcium homeostasis during mycelium-to-yeast dimorphism of Paracoccidioides brasiliensis
dc.typeOtro


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