title: In vitro activity of calcineurin and heat shock protein 90 Inhibitors against Aspergillus fumigatus azole- and echinocandin-resistant strains.
abstract: Due to the limited number of antifungals and the emergence of resistance, new therapies against invasive aspergillosis are needed. We show that calcineurin inhibitors are active in vitro against both azole- and echinocandin-resistant Aspergillus fumigatus strains. The heat shock protein 90 (Hsp90) inhibitor geldanamycin had modest activity when used alone, but its combination with caspofungin or tacrolimus (FK506) resulted in fungicidal activity against azole-resistant strains. Targeting the Hsp90-calcineurin axis is a promising alternative strategy against azole-resistant A. fumigatus strains.
authors.affiliation: Division of Pediatric Infectious Diseases, Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lamoth
authors.forename: Praveen R
authors.initials: PR
authors.lastname: Juvvadi
authors.forename: Christopher
authors.initials: C
authors.lastname: Gehrke
authors.forename: William J
authors.initials: WJ
authors.lastname: Steinbach
mesh_terms: D000935:Antifungal Agents / Q000494:pharmacology*; D001228:Aspergillosis / Q000188:drug therapy / Q000382:microbiology; D001232:Aspergillus fumigatus / Q000187:drug effects*; D001393:Azoles / Q000494:pharmacology; D016227:Benzoquinones / Q000494:pharmacology; D065095:Calcineurin Inhibitors; D000077336:Caspofungin; D026141:Drug Resistance, Multiple, Fungal; D004359:Drug Therapy, Combination; D054714:Echinocandins / Q000494:pharmacology; D018841:HSP90 Heat-Shock Proteins / Q000037:antagonists & inhibitors*; D047029:Lactams, Macrocyclic / Q000494:pharmacology; D055666:Lipopeptides; D008826:Microbial Sensitivity Tests; D016559:Tacrolimus / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D001393:Azoles; D016227:Benzoquinones; D065095:Calcineurin Inhibitors; D054714:Echinocandins; D018841:HSP90 Heat-Shock Proteins; D047029:Lactams, Macrocyclic; D055666:Lipopeptides; D000077336:Caspofungin; D016559:Tacrolimus; C001277:geldanamycin