Activity of Sanguinarine against Candida albicans Biofilms
Activity of Sanguinarine against Candida albicans Biofilms
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血根碱对抗白色念珠菌生物膜的活性
DOI：
10.1128/aac.02259-16
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发表时间：
2017-05-01
影响因子：
4.9
通讯作者：
Wang, Yan
中科院分区：
文献类型：
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作者：
Zhong, Hua;Hu, Dan-Dan;Wang, Yan
白色念珠菌生物膜对许多临床抗真菌药物具有耐药性，在白色念珠菌感染过程中起着重要的作用。迫切需要新的抗白色念珠菌生物膜的抗真菌药物。本研究的目的是评价血根碱（SAN）对白色念珠菌生物膜的活性，并探讨其潜在的机制。SAN的MIC50为3.2 μ g/ml，而>= 0.8 μ g/ml的SAN可抑制白色念珠菌生物膜。进一步研究发现，>0.8 μ g/ml的SAN可以降低细胞表面疏水性（CSH），抑制菌丝的形成。实时逆转录pcr （RT-PCR）结果显示，暴露于SAN的白色念珠菌抑制了一些与环AMP （cAMP）通路相关的粘附和菌丝特异性/必需基因的表达，包括ALS3、HWP1、ECE1、HGC1和CYR1。同样，在SAN处理后，白色念珠菌的内源性cAMP水平下调，cAMP的加入挽救了SAN诱导的丝缺陷。此外，SAN对人脐静脉内皮细胞的毒性较低，50%抑制浓度（IC50）为7.8 μ g/ml。综上所述，SAN对白色念珠菌生物膜表现出较强的活性，其活性与cAMP通路抑制对粘连和菌丝形成的抑制作用有关。
Candida albicans biofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process of C. albicans infections. New antifungal agents against C. albicans biofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity against Candida albicans biofilms and explore the underlying mechanism. The MIC50 of SAN was 3.2 mu g/ml, while >= 0.8 mu g/ml of SAN could suppress C. albicans biofilms. Further study revealed that >0.8 mu g/ml of SAN could decrease cellular surface hydrophobicity (CSH) and inhibited hypha formation. Real-time reverse transcription-PCR (RT-PCR) results indicated that the exposure of C. albicans to SAN suppressed the expression of some adhesion-and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, including ALS3, HWP1, ECE1, HGC1, and CYR1. Consistently, the endogenous cAMP level of C. albicans was downregulated after SAN treatment, and the addition of cAMP rescued the SAN-induced filamentation defect. In addition, SAN showed relatively low toxicity to human umbilical vein endothelial cells, the 50% inhibitory concentration (IC50) being 7.8 mu g/ml. Collectively, the results show that SAN exhibits strong activity against C. albicans biofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.