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首页> 外文期刊>Journal of Medical Microbiology: An Official Journal of the Pathological Society of Great Britain and Ireland >Synergistic mechanism for tetrandrine on fluconazole against Candida albicans through the mitochondrial aerobic respiratory metabolism pathway
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Synergistic mechanism for tetrandrine on fluconazole against Candida albicans through the mitochondrial aerobic respiratory metabolism pathway

机译：通过线粒体有氧呼吸新陈代谢途径对念珠菌对念珠菌对念珠菌对念珠菌的协同机制

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We found that tetrandrine (TET) can reverse the resistance of Candida albicans to fluconazole (FLC) and that this interaction is associated with the inhibition of drug efflux pumps. Mitochondrial aerobic respiration, which plays a major role in C. albicans metabolism, is the primary source of ATP for cellular processes, including the activation of efflux pumps. However, it was unclear if TET exerts its synergistic action against C. albicans via its impact on the mitochondrial aerobic respiratory metabolism. To investigate this mechanism, we examined the impact of FLC in the presence or absence of TET on two C. albicans strains obtained from a single parental source (FLC-sensitive strain CA-1 and FLC-resistant strain CA-16). We analysed key measures of energy generation and conversion, including the activity of respiration chain complexes I and III (CI and CIII), ATP synthase (CV) activity, and the generation of reactive oxygen species (ROS), and studied intracellular ATP levels and the mitochondrial membrane potential (ΔΨm), which has a critical impact on energy transport. Mitochondrial morphology was observed by confocal microscopy. Our functional analyses revealed that, compared with strains treated only with FLC, TET+FLC increased the ATP levels and decreased ΔΨm in CA-1, but decreased ATP levels and increased ΔΨm in CA-16 (P&0.05). Additionally, CI, CIII and CV activity decreased by 23–48 %. The production of ROS increased by two- to threefold and mitochondrial morphology was altered in both strains. Our data suggested that TET impacted mitochondrial aerobic respiratory metabolism by influencing the generation and transport of ATP, reducing the utilization of ATP, and resulting in the inhibition of drug efflux pump activity. This activity contributed to the synergistic action of TET on FLC against C. albicans.
机译：我们发现，Tetrandrine（Tet）可以逆转Candida醛糖蛋白对氟康唑（FLC）的阻力，并且这种相互作用与抑制药物流出泵有关。线粒体有氧呼吸在C. albicans代谢中起主要作用，是用于细胞过程的ATP的主要来源，包括Efflux泵的激活。然而，如果TET通过其对线粒体有氧呼吸道代谢的影响，TET尚不清楚TET对C. albicans的协同作用。为了研究这种机制，我们在两种父母源（FLC敏感菌株CA-1和FLC抗性菌株CA-16）中，检查了FLC在两种C.醛糖苷菌株的存在或不存在TET中的影响。我们分析了能量产生和转化的关键措施，包括呼吸链复合物I和III（CI和CIII），ATP合酶（CV）活性的活性，以及​​反应性氧物种（ROS）的产生，并研究了细胞内ATP水平和线粒体膜电位（δψm），对能量运输具有关键影响。通过共聚焦显微镜观察线粒体形态。我们的功能分析显示，与仅用FLC处理的菌株相比，TET + FLC增加了ATP水平并在CA-1中降低Δεm，但在Ca-16中降低并增加Δψm（P <0.05）。此外，CI，CIII和CV活性降低23-48％。在两种菌株中改变了两到三倍和线粒体形态的ROS的生产。我们的数据表明TET通过影响ATP的产生和运输，降低ATP的利用，并导致抑制药物流出泵活性，产生线粒体有氧呼吸代谢。该活动有助于TET对FLC对抗C. albicans的协同作用。

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