菌物学报2025，Vol.44Issue(1)：93-102,10.DOI:10.13346/j.mycosystema.240181
烟曲霉ERG3基因在米诺环素与唑类药物协同抗烟曲霉中的机制
Mechanism of synergistic antifungal activity of minocycline and azole drugs mediated by ERG3 gene in Aspergillus fumigatus
摘要
Abstract
Minocycline(MIN),a type of tetracycline used as an antibiotic,is utilized for treatment of various infectious ailments.A previous investigation of ours demonstrated that when minocycline was combined with azoles,it exhibited antifungal properties against Aspergillus fumigatus.Ergosterol is an important component of the fungal cell membrane,and the ERG3 gene encodes a key enzyme for the late stages of the ergosterol synthesis pathway(sterol△5,6-desaturase).In this research the △ERG3 mutant was obtained by knocking out the ERG3 gene of A.fumigatus.The M38 A2 method was used to detect the sensitivity changes of △ERG3 and wild-type WT(△KU80,pyrG+)in combination of MIN and azoles[posaconazole(POS),and itraconazole(ITR),and voriconazole(VOR)]against Aspergillus fumigatus.The results showed that when MIN and POS were combined,the minimum inhibitory concentration(MIC)value of POS against WT was 0.031 25 μg/mL,and the fractional inhibitory concentration index(FICI)value was 0.187 5,indicating a synergistic effect between MIN and POS.The MIC value and FICI value of POS for the knockout strain △ERG3 were 1 μg/mL and 2,respectively.MIN and POS showed no synergistic effect.The results of the paper method indicate that the diameter of the inhibition zone of △ERG3 in the combination treatment group(MIN+POS)or single drug treatment group(POS)is significantly smaller as compared with the inhibition zone generated by WT,showing statistically significant difference(P＜0.05).This implies that eliminating ERG3 gene could reduce the synergistic effect between MIN and POS.No significant distinction in ergosterol production was observed between WT treated by combination of POS and MIN,and that singly treated by POS.However,a marked decrease in ergosterol production was observed in△ERG3 under combined treatment of POS and MIN(P＜0.05).Reactive oxygen species(ROS)production by △ERG3 was significantly less than that by WT under monotherapy of POS or combination of POS+MIN.Therefore,ERG3 participates in the synergistic effect pathway of MIN and azole drugs against A.fumigatus.This study provides a new theoretical basis for investigating the mechanism of the synergistic antifungal effect under combination of minocycline and azoles.关键词
烟曲霉/ERG3基因/米诺环素/泊沙康唑Key words
Aspergillus fumigatus/ERG3 gene/minocycline/posaconazole引用本文复制引用
周晔,张恒,龚霄,孙毅,高露娟..烟曲霉ERG3基因在米诺环素与唑类药物协同抗烟曲霉中的机制[J].菌物学报,2025,44(1):93-102,10.基金项目
福建省自然科学基金(2021D031) （2021D031）
厦门市科技局医疗卫生指导性项目(3502Z202114ZD1072) （3502Z202114ZD1072）
湖北省重点研发项目(2022BCE022)This work was supported by the Fujian Provincial Natural Science Foundation(2021D031),the Medical and Health Guidance Project of Xiamen Science and Technology Bureau(3502Z202114ZD1072),and the Key Research and Development Project of Hubei Province(2022BCE022). （2022BCE022）
