Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism.
Pyrogallol and Fluconazole Interact Synergistically In Vitro against Candida glabrata through an Efflux-Associated Mechanism.
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连苯三酚和氟康唑通过外排相关机制在体外协同作用对抗光滑念珠菌
DOI：
10.1128/aac.00100-21
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发表时间：
2021-06-17
影响因子：
4.9
通讯作者：
Hu X
中科院分区：
文献类型：
--
作者：
Yao D;Zhang G;Chen W;Chen J;Li Z;Zheng X;Yin H;Hu X
光滑念珠菌是目前世界上最常见的非白念珠菌菌种。念珠菌耐药性的潜在严重性要求发现新的抗真菌药物，包括那些可以用于联合治疗的药物。光滑念珠菌是目前世界上最常见的非白念珠菌属中的第一或第二种。念珠菌耐药性的潜在严重性要求发现新的抗真菌药物，包括那些可以用于联合治疗的药物。在这项研究中，我们评估了邻苯三酚(PG)和唑类药物对22株临床分离的光滑念珠菌的体外相互作用。用罗丹明6G外排法和定量逆转录聚合酶链式反应(QRT-PCR)研究了PG与氟康唑(FLC)协同作用的可能机制。在药敏试验中，PG与FLC、伊曲康唑和伏立康唑有很强的协同作用，其分数抑菌浓度指数分别为0.18~0.375、0.250~0.750和0.141~0.750。与单独加入PG或FLC培养的细胞相比，PG+FLC培养的细胞罗丹明6G排泄减少，外排相关基因CgCDR1、CgCDR2和CgPDR1的表达显著下调。PG在与ΔCgpdr1株的对照试验中并未增强FLC。CgPDR1功能等位基因的恢复也恢复了协同作用。这些结果表明，PG是一种协同增强咪唑类化合物活性的抗真菌药物。此外，PG似乎通过抑制外排泵和下调CgCDR1、CgCDR2和CgPDR1来发挥其作用，其中CgPDR1可能在这一过程中发挥关键作用。
Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. ABSTRACT Candida glabrata is currently the first or second most commonly encountered non-albicans Candida species worldwide. The potential severity of Candida resistance mandates the discovery of novel antifungal agents, including those that can be used in combination therapies. In this study, we evaluated the in vitro interactions of pyrogallol (PG) and azole drugs against 22 clinical C. glabrata isolates. The potential mechanism underlying the synergism between PG and fluconazole (FLC) was investigated by the rhodamine 6G efflux method and quantitative reverse transcription (qRT)-PCR analysis. In susceptibility tests, PG showed strong synergism with FLC, itraconazole (ITC), and voriconazole (VRC), with fractional inhibitory concentration index values of 0.18 to 0.375 for PG+FLC, 0.250 to 0.750 for PG+ITC, and 0.141 to 0.750 for PG+VRC. Cells grown in the presence of PG+FLC exhibited reduced rhodamine 6G extrusion and significantly downregulated expression of the efflux-related genes CgCDR1, CgCDR2, and CgPDR1 compared with cells grown in the presence of PG or FLC alone. PG did not potentiate FLC when tested against a ΔCgpdr1 strain. Restoration of a functional CgPDR1 allele also restored the synergism. These results indicate that PG is an antifungal agent that synergistically potentiates the activity of azoles. Furthermore, PG appears to exert its effects by inhibiting efflux pumps and downregulating CgCDR1, CgCDR2, and CgPDR1, with CgPDR1 probably playing a crucial role in this process.