Study of the function of calcineurin in acquired resistance of Trichosporonasahii to fluconazole

doi:10.11786/sypfbxzz.1674-1293.20180506

Abstract：Objective To investigate the role of calcineurin in the acquired resistance of T. asahii to fluconazole, which induced by the gradient concentration of fluconazole combined with calcineurin inhibitor(cyclosporin A). Methods The standard strain CBS2479 was induced by gradient concentration of fluconazole, gradient concentration of fluconazole combined with cyclosporin A, cyclosporin A respectively; and the MIC value of fluconazole was detected during the induction stage, and the sensitivity of the common triazole antifungal agents was detected by the induction end point. After that, fluconazole-resistant strains cultured on non-drug medium for 20 generations(the MIC value of each strain was detected in every four generation), and the stability of drug resistance phenotype was observed. Results After the induction by gradient concentration of fluconazole, group A(gradient concentration of fluconazole combined with fixed concentration of cyclosporin A) and group B(gradient concentration of fluconazole) could obtain fluconazole-resistant strain, and the MIC value of fluconazole in group A was lower than that of group B. Comparing with the initial strain, the increased level of MIC value of itraconazole and voriconazole for group A was lower than group B. After having been cultured on non-drug medium for 20 generations, the fluconazole resistance in the group A was unstable and the MIC value of fluconazole, itraconazole and voriconazole was recovered or near the initial state, while the resistance of group B to fluconazole, itraconazole and voriconazole was stable. Conclusion Calcineurin plays a certain role in the acquired resistance of T. asahii to the fluconazole, and the application of calcineurin inhibitor can partially inhibit the occurrence of adaptive resistance phenotype, and this phenotype can be converted after the removal of stress pressure, so this formula may be a potential strategy to reduce the long-term application of fluconazole indued fluconazole resistance of T. asahii.