{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:47:33Z","timestamp":1790628453062,"version":"4.1.0"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"10","license":[{"start":{"date-parts":[[2008,10,1]],"date-time":"2008-10-01T00:00:00Z","timestamp":1222819200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Eukaryot Cell"],"published-print":{"date-parts":[[2008,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:italic>Paracoccidioides brasiliensis<\/jats:italic>\n            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\u00b0C to 37\u00b0C and is critical for pathogenicity. Intracellular Ca\n            <jats:sup>2+<\/jats:sup>\n            levels increased in hyphae immediately after temperature-induced dimorphism. The chelation of Ca\n            <jats:sup>2+<\/jats:sup>\n            with extracellular (EGTA) or intracellular (BAPTA) calcium chelators inhibited temperature-induced dimorphism, whereas the addition of extracellular Ca\n            <jats:sup>2+<\/jats:sup>\n            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\n            <jats:italic>P. brasiliensis<\/jats:italic>\n            . 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\n            <jats:sup>2+<\/jats:sup>\n            homeostasis and decreased mRNA transcription of the\n            <jats:italic>CCH1<\/jats:italic>\n            gene for the plasma membrane Ca\n            <jats:sup>2+<\/jats:sup>\n            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\n            <jats:sup>2+<\/jats:sup>\n            \/calmodulin-dependent phosphatase calcineurin controls hyphal and yeast morphology, M-Y dimorphism, growth, and Ca\n            <jats:sup>2+<\/jats:sup>\n            homeostasis in\n            <jats:italic>P. brasiliensis<\/jats:italic>\n            and that CsA is an effective chemical block for thermodimorphism in this organism. The effects of calcineurin inhibitors on\n            <jats:italic>P. brasiliensis<\/jats:italic>\n            reinforce the therapeutic potential of these drugs in a combinatory approach with antifungal drugs to treat endemic paracoccidioidomycosis.\n          <\/jats:p>","DOI":"10.1128\/ec.00110-08","type":"journal-article","created":{"date-parts":[[2008,9,6]],"date-time":"2008-09-06T00:56:03Z","timestamp":1220662563000},"page":"1856-1864","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":42,"title":["Evidence for the Role of Calcineurin in Morphogenesis and Calcium Homeostasis during Mycelium-to-Yeast Dimorphism of\n            <i>Paracoccidioides brasiliensis<\/i>"],"prefix":"10.1128","volume":"7","author":[{"given":"Claudia B. L.","family":"Campos","sequence":"first","affiliation":[{"name":"Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, Sao Paulo, 12244-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joao Paulo T.","family":"Di Benedette","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, Sao Paulo, 12244-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Flavia V.","family":"Morais","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, Sao Paulo, 12244-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Ovalle","sequence":"additional","affiliation":[{"name":"Department of Biology, Brooklyn College of the City University of New York, New York 11210"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina P.","family":"Nobrega","sequence":"additional","affiliation":[{"name":"Instituto de Pesquisa e Desenvolvimento, Universidade do Vale do Paraiba (UNIVAP), Sao Jose dos Campos, Sao Paulo, 12244-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.2.3.422-430.2003"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.73.9.5767-5774.2005"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/21.10.2343"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.5.1020"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-291X(03)01552-3"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fgb.2006.08.004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1087-1845(03)00044-6"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004380100586"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1080\/02681218780000021"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.15.8.4103"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00248-07"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/341758a0"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00437630"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.87.11.4028"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/EC.00158-06"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_3_2_18_2","first-page":"305","volume":"26","year":"1995","unstructured":"McEwen, J. 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