Effects of geldanamycin and cyclosporine combined with antifungal drugs against clinical Trichosporon asahii isolates in vitro
Abstract：Objective lnvasive trichosporonosis is associated with a high mortality rate and the emergence of MDR Trichosporon.Asahii(T.asahii) is of particular concern.Heat shock protein 90(Hsp90) and its client protein,calcineurin,represent an important pathway for fungal drug resistance.We investigated the antifungal activity of compounds targeting the Hsp90-calcineurin axis against T.asahii.Methods The in vitro antifungal activity of geldanamycin(the Hsp90 inhibitor) and cyclosporine A(anti-calcineurin drug) were assessed by the standard broth dilution method against 21 clinical isolates of T.asahii.Results Geldanamycin had good antifungal activity,while cyclosporine A had little antifungal activity against different T.asahii isolates.Moreover,both geldanamycin and cyclosporine A exhibited synergistic interactions with five antifungals(fluconazole,itraconazole,voriconazole,amphotericin B and caspofungin) against T.asahii.Conclusion Inhibitors targeting the Hsp90-calcineurin axis(geldanamycin and cyclosporine A) can increase the susceptibility of antifungals to T.asahii,which is suggested as a promising antifungal strategy against invasive trichosporonosis.
Keywords：Trichosporon asahiiDrug interactionHeat shock protein 90CalcineurinGeldanamycinCyclosporine
Publication Date：2018-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 67-70 )