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Drug resistance during<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>infection is common and constitutes a significant therapeutic challenge. The calcineurin inhibitor FK506 exhibits synergistic fungicidal activity with azoles or echinocandins in the fungal pathogens<jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>,<jats:named-content content-type=\"genus-species\">Cryptococcus neoformans<\/jats:named-content>, and<jats:named-content content-type=\"genus-species\">Aspergillus fumigatus<\/jats:named-content>. In this study, we show that calcineurin is required for cell wall integrity and wild-type tolerance of<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>to azoles and echinocandins; hence, these drugs are candidates for combination therapy with calcineurin inhibitors. In contrast to<jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>, in which the roles of calcineurin and Crz1 in hyphal growth are unclear, here we show that calcineurin and Crz1 play a clearly demonstrable role in hyphal growth in response to nutrient limitation in<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>. We further demonstrate that thigmotropism is controlled by Crz1, but not calcineurin, in<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>. Similar to<jats:named-content content-type=\"genus-species\">C. albicans<\/jats:named-content>,<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>calcineurin enhances survival in serum.<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>calcineurin and<jats:named-content content-type=\"genus-species\">crz1\/crz1<\/jats:named-content>mutants exhibit attenuated virulence in a murine systemic infection model, likely attributable to defects in cell wall integrity, hyphal growth, and serum survival. Furthermore, we show that<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>calcineurin mutants are unable to establish murine ocular infection or form biofilms in a rat denture model. That calcineurin is required for drug tolerance and virulence makes fungus-specific calcineurin inhibitors attractive candidates for combination therapy with azoles or echinocandins against emerging<jats:named-content content-type=\"genus-species\">C. dubliniensis<\/jats:named-content>infections.<\/jats:p>","DOI":"10.1128\/ec.00310-10","type":"journal-article","created":{"date-parts":[[2011,4,30]],"date-time":"2011-04-30T03:10:45Z","timestamp":1304133045000},"page":"803-819","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":106,"title":["Calcineurin Controls Drug Tolerance, Hyphal Growth, and Virulence in Candida dubliniensis"],"prefix":"10.1128","volume":"10","author":[{"given":"Ying-Lien","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Brand","sequence":"additional","affiliation":[{"name":"Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma L.","family":"Morrison","sequence":"additional","affiliation":[{"name":"Aberdeen Fungal Group, School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fitz Gerald S.","family":"Silao","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Parasitology, University of Perpetual Help-Dr. Jose G. 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