Involvement of mitochondrial aerobic respiratory activity in efflux-mediated resistance of C. albicans to fluconazole
Involvement of mitochondrial aerobic respiratory activity in efflux-mediated resistance of C. albicans to fluconazole
复制标题
线粒体有氧呼吸活动参与外排介导的白色念珠菌对氟康唑耐药性
DOI：
10.1016/j.mycmed.2017.04.004
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发表时间：
2017-09-01
影响因子：
3.6
通讯作者：
Zhang, H.
中科院分区：
文献类型：
--
作者：
Guo, H.;Xie, S. M.;Zhang, H.
外排泵介导的细胞内药物蓄积减少是白念珠菌对氟康唑耐药的重要机制之一。白色念珠菌）。此外，线粒体有氧呼吸在C.白色念珠菌代谢然而，线粒体有氧呼吸是否参与外排介导的耐药性尚不清楚。白色念珠菌到唑类。我们测量了能量转换的关键参数，包括呼吸链复合物I，III和V（CI，CIII和CV）的活性，以及两个C中的活性氧（ROS）。从单一亲本来源获得的白色念珠菌菌株（FLC敏感菌株CA-1（s）和FLC抗性菌株CA-16（R））。此外，我们定量了细胞内ATP水平和线粒体膜电位（Δ psi m），这对能量转运具有关键影响。我们的分析显示CA-16（R）中的ATP水平和Δ psi m高于CA-1（s）（P < 0.05），并且Sc 5314（s）（FLC敏感株）中的ATP水平和Δ psi m高于Sc 5314（R）（FLC抗性株）。CA-16（R）中CI和CV活性增加，Sc 5314（R）中CI、CIII和CV活性增加。此外，与其各自的易感对应物相比，CA-16 R和Sc 5314（R）中的ROS减少。我们的数据表明，线粒体有氧呼吸代谢可能直接与外流介导的阻力的C。白念珠菌与白念珠菌菌株之间的相互作用可能通过改变线粒体有氧呼吸代谢，增加ATP产生和减少ROS产生，增强外排泵的活性，从而降低对FLC的敏感性。(C)2017 Elsevier Masson SAS。图斯所有权保留。
Reduced intracellular accumulation of drugs mediated by efflux pump is one of the most critical mechanisms governing fluconazole (FLC) resistance in Candida albicans (C. albicans). Besides, mitochondrial aerobic respiration plays a major role in C. albicans metabolism. However, it is unclear whether mitochondrial aerobic respiration is involved with efflux-mediated resistance of C. albicans to azole. We measured key parameters of energy conversion, including the activity of respiratory chain complexes I, III and V (CI, CIII and CV), and reactive oxygen species (ROS) in two C. albicans strains (FLC-susceptible strain CA-1(s) and FLC-resistant strain CA-16(R)) obtained from a single parental source. Additionally, we quantified intracellular ATP levels and mitochondrial membrane potential (Delta psi m), which has critical effect on energy transport. Our analyses revealed a higher ATP level and Delta psi m in CA-16(R) compared with CA-1(s) (P < 0.05), and a higher ATP level and Delta psi m in Sc5314(s) (FLC-susceptible strain) compared with Sc5314(R) (FLC-resistant strain). CI and CV activity increased in CA-16(R), activity of CI, CIII and CV increased in Sc5314(R). Additionally, ROS decreased in CA-16R and Sc5314(R) compared with their respective susceptible counterparts. Our data suggest that mitochondrial aerobic respiratory metabolism might be directly associated with the efflux-mediated resistance of C. albicans to albicans strains might enhance the activity of efflux pumps and therefore decrease sensitivity to FLC through alteration of mitochondrial aerobic respiratory metabolism, by increased ATP production and decreased ROS generation. (C) 2017 Elsevier Masson SAS. Tous droits reserves.