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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  ORF19.273  in  Candida albicans , is found to be involved in the inhibition of 14α-methylated sterols and resistance to azoles. Under the action of fluconazole,  nsg2 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  NSG2  plays an important role in  C. albicans  responding to azoles  in vitro  as well as  in vivo . These phenotypes are completely different from those of Nsg2p in  Saccharomyces cerevisia 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  C. albicans , which may provide new strategies for overcoming the problems of azole resistance.

NSG2 (ORF19.273) Encoding Protein Controls Sensitivity of Candida albicans to Azoles through Regulating the Synthesis of C14-Methylated Sterols