菌物学报2025，Vol.44Issue(12)：92-105,14.DOI:10.13346/j.mycosystema.250158
ABCM基因介导烟曲霉中米诺环素-唑类协同抗真菌作用
ABCM gene mediates the synergistic antifungal effects of minocycline and azole in Aspergillus fumigatus
摘要
Abstract
Minocycline(MIN),a second-generation semi-synthetic tetracycline antibiotic,potent synergistic antifungal activity against Aspergillus fumigatus when combined with azoles.The ABCM gene(GenBank ID:AFUA_4G09150)encodes an ABC transporter protein.In this study,the ABCM knockout strain(ΔABCM)of A.fumigatus was successfully constructed.Susceptibility changes of ΔABCM and wild-type(WT)strains to MIN-triazole combinations were evaluated using in vitro antifungal susceptibility test according to the CLSI M38-A3 guideline and the disk diffusion assay.Results demonstrated that deletion of ABCM abolished the synergistic effect between MIN and posaconazole(POS),as reflected by the fractional inhibitory index(FICI)values(WT:FICI=0.156 vs.ΔABCM:FICI=0.625).Disk diffusion assays revealed significantly smaller inhibition zones for the ΔABCM strain as compared with WT when treated with MIN-POS combinations(P<0.05),indicating loss of synergy upon ABCM deletion.Further investigations showed that MIN-POS treatment induced significantly lower reactive oxygen species(ROS)production in ΔABCM as compared with that in WT(P<0.05).In comparison with WT,ΔABCM exhibited higher rhodamine 6G fluorescence intensity and enhanced tolerance to oxidative stressors menadione under MIN-POS co-treatment(P<0.05).These findings suggest that the ABCM gene may serve as a critical target mediating the synergistic antifungal effects of MIN and POS,and its deletion disrupts this synergy.Additionally,ABCM gene expression may reduce external resistance.This study advances the understanding of the synergistic antifungal mechanism of MIN and azoles,offering a new theoretical foundation for elucidating A.fumigatus drug resistance.关键词
ABC转运蛋白/烟曲霉/ABCM基因/分级抑菌浓度Key words
ABC transporter protein/Aspergillus fumigatus/ABCM gene/graded inhibitory concentration引用本文复制引用
LI Juncheng,HU Jing,CHEN Tian,ZHOU Ye,ZHANG Heng,SUN Yi..ABCM基因介导烟曲霉中米诺环素-唑类协同抗真菌作用[J].菌物学报,2025,44(12):92-105,14.基金项目
荆州市科技计划(2024HD34) （2024HD34）
长江大学科技援助西藏医学人才培养计划(2023YZ06) （2023YZ06）
湖北省重点研发计划(2024BCB043)This work was supported by the Jingzhou Science and Technology Project(2024HD34),the Yangtze University Science and Technology Assistance Program for Medical Talent Cultivation in Xizang(2023YZ06),and the Hubei Provincial Key Research and Development Program(2024BCB043). （2024BCB043）
