() Encoding Protein Controls Sensitivity of to Azoles through Regulating the Synthesis of C14-Methylated Sterols.

Antifungal azole drugs inhibit the synthesis of ergosterol and cause the accumulation of sterols containing a 14α-methyl group, which is related to the properties of cell membrane. Due to the frequent recurrence of fungal infections and clinical long-term prophylaxis, azole resistance is increasing rapidly. In our research, Nsg2p, encoded by the in , is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles. Under the action of fluconazole, Δ/Δ mutants are seriously damaged in the integrity and functions of cell membranes with a decrease of ergosterol ratio and an increase of both obtusifoliol and 14α-methylfecosterol ratio. The balance between ergosterol and 14α-methyl sterols mediated by plays an important role in responding to azoles as well as . These phenotypes are completely different from those of Nsg2p in e, which is proved to increase the stability of HMG-CoA and resistance to lovastatin. Based on the evidence above, it is indicated that the decrease of 14α-methylated sterols is an azole-resistant mechanism in , which may provide new strategies for overcoming the problems of azole resistance.