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维拉帕米对白色念珠菌菌丝发育、黏附及胃肠道定植的抑制作用。

Inhibitory effect of verapamil on Candida albicans hyphal development, adhesion and gastrointestinal colonization.

作者信息

Yu Qilin, Ding Xiaohui, Zhang Bing, Xu Ning, Jia Chang, Mao Jiwei, Zhang Biao, Xing Laijun, Li Mingchun

机构信息

Key Laboratory of Molecular Microbiology and Technology, Ministry of Education, College of Life Science, Nankai University, Tianjin, China.

出版信息

FEMS Yeast Res. 2014 Jun;14(4):633-41. doi: 10.1111/1567-1364.12150. Epub 2014 Apr 3.

Abstract

Candida albicans morphogenesis and gastrointestinal colonization are closely associated with the pathogenicity of this pathogen. This study investigated the in vitro and in vivo effect of verapamil, a calcium channel blocker, on these processes. Exposure to ≥ 10 μg mL(-1) verapamil led to a significant decrease of C. albicans hyphal cells. The ability to adhere to a polystyrene surface and buccal epithelial cells was inhibited by exposure to ≥ 20 μg mL(-1) verapamil. Detection of the Hwp1-green fluorescent protein fusion protein showed that verapamil inhibited expression and transport of Hwp1, indicating its activity against both the regulation network of morphogenesis-associated proteins and the secretory pathway in C. albicans. Moreover, treatment with verapamil at 10 mg (kg day)(-1) led to a remarkable decrease in gastrointestinal-colonizing fungal cells. This study revealed the inhibitory effect of verapamil on C. albicans hyphal development, adhesion and gastrointestinal colonization, which is relevant to decreased expression and abnormal transport of the proteins required for morphogenesis. Therefore, verapamil may be taken into account when choosing an antifungal therapy against C. albicans colonization and infection.

摘要

白色念珠菌的形态发生和胃肠道定植与该病原体的致病性密切相关。本研究调查了钙通道阻滞剂维拉帕米在体外和体内对这些过程的影响。暴露于≥10μg/mL的维拉帕米会导致白色念珠菌菌丝细胞显著减少。暴露于≥20μg/mL的维拉帕米会抑制其黏附聚苯乙烯表面和颊上皮细胞的能力。对Hwp1-绿色荧光蛋白融合蛋白的检测表明,维拉帕米抑制了Hwp1的表达和转运,这表明其对白色念珠菌形态发生相关蛋白的调控网络和分泌途径均有活性。此外,以10mg/(kg·天)的剂量用维拉帕米治疗会导致胃肠道定植真菌细胞显著减少。本研究揭示了维拉帕米对白色念珠菌菌丝发育、黏附及胃肠道定植的抑制作用,这与形态发生所需蛋白质的表达降低和转运异常有关。因此,在选择针对白色念珠菌定植和感染的抗真菌治疗时,可考虑使用维拉帕米。

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