去乙酰化酶抑制剂AK-1对氟康唑体外抑制白念珠菌生长的影响

doi:10.35541/cjd.20240668

Abstract

Abstract: 【Abstract】 Objective To investigate the effect of the deacetylase inhibitor AK-1 on the antifungal activity of fluconazole （FCZ） against Candida albicans （C. albicans）. Methods RPMI-1640 media containing FCZ at different concentrations of 0.0625 - 32 μg/ml were prepared. C. albicans strains were inoculated onto the medium plates, and the growth was observed after 24 hours. The inhibitory effects on fungal growth were assessed after 24-hour treatment with or without 75 μmol/L AK-1 （+/-）, solvent dimethyl sulfoxide （DMSO）（+/-）, and low concentrations of FCZ （0.0625, 0.125 μg/ml）（+/-）. Western blot analysis was performed to evaluate the effects of AK-1 and FCZ on acetylation and crotonylation modifications in C. albicans, and normalized relative levels of acetylation and crotonylation modifications were calculated with the values of the blank group （AK-1-/DMSO-/FCZ- group） set as the baseline value of 1. One-way analysis of variance was used for comparisons among multiple groups, and the least significant difference-t test for multiple comparisons. Results FCZ at concentrations of 0.125 - 32 μg/ml markedly inhibited the growth of C. albicans. Co-treatment with DMSO and FCZ （AK-1-/DMSO+/FCZ+ group） resulted in stronger inhibition of fungal growth compared with the FCZ treatment alone （AK-1-/DMSO-/FCZ+ group）. However, the addition of AK-1 （AK-1+/DMSO+/FCZ+ group） reversed the inhibitory effect of DMSO and FCZ on fungal growth. Further experiments demonstrated that both acetylation （0.766 ± 0.055） and crotonylation levels （0.856 ± 0.032） were significantly reduced （both P < 0.05） in the AK-1-/DMSO-/FCZ+ group （0.0625 μg/ml FCZ treatment alone） compared with the blank group; co-treatment with DMSO and FCZ （AK-1-/DMSO+/FCZ+ group） further decreased acetylation （0.501 ± 0.073） and crotonylation levels （0.723 ± 0.044） compared with FCZ treatment alone （both P < 0.05）; the AK-1+/DMSO+/FCZ+ group showed increased acetylation （0.846 ± 0.014） and crotonylation levels （1.325 ± 0.119） compared with the AK-1-/DMSO+/FCZ+ group, while exhibited significantly lower acetylation levels but significantly higher crotonylation levels than the blank group （both P < 0.05）. Conclusion The deacetylase inhibitor AK-1 may reverse the inhibitory effect of FCZ on C. albicans by regulating acetylation and crotonylation modifications.

Key words: Candida albicans, Fluconazole, Sirtuin 2 inhibitor, AK-1, Acetylation, Crotonylation

Zhou Xiaowei, Mei Huan, Liu Weida, Li Xiaofang, . Effect of the deacetylase inhibitor AK-1 on the in vitro activity of fluconazole against Candida albicans[J]. Chinese Journal of Dermatology, 2025, 58(12): 1141-1147.doi:10.35541/cjd.20240668

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Effect of the deacetylase inhibitor AK-1 on the in vitro activity of fluconazole against Candida albicans

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