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血根碱对白色念珠菌生物膜的活性。

Activity of Sanguinarine against Candida albicans Biofilms.

作者信息

Zhong Hua, Hu Dan-Dan, Hu Gan-Hai, Su Juan, Bi Shuang, Zhang Zhuo-Er, Wang Zheng, Zhang Ri-Li, Xu Zheng, Jiang Yuan-Ying, Wang Yan

机构信息

School of Pharmacy, Second Military Medical University, Shanghai, China.

Department of Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

出版信息

Antimicrob Agents Chemother. 2017 Apr 24;61(5). doi: 10.1128/AAC.02259-16. Print 2017 May.

Abstract

biofilms show resistance to many clinical antifungal agents and play a considerable contributing role in the process of infections. New antifungal agents against biofilms are sorely needed. The aim of this study was to evaluate sanguinarine (SAN) for its activity against biofilms and explore the underlying mechanism. The MIC of SAN was 3.2 μg/ml, while ≥0.8 μg/ml of SAN could suppress biofilms. Further study revealed that ≥0.8 μg/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 to SAN suppressed the expression of some adhesion- and hypha-specific/essential genes related to the cyclic AMP (cAMP) pathway, including , , , , and Consistently, the endogenous cAMP level of 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 (IC) being 7.8 μg/ml. Collectively, the results show that SAN exhibits strong activity against biofilms, and the activity was associated with its inhibitory effect on adhesion and hypha formation due to cAMP pathway suppression.

摘要

生物膜对许多临床抗真菌药物具有抗性,并在感染过程中起相当大的作用。因此,迫切需要新型抗生物膜的抗真菌药物。本研究旨在评估血根碱(SAN)对生物膜的活性,并探讨其潜在机制。SAN的最低抑菌浓度(MIC)为3.2μg/ml,而≥0.8μg/ml的SAN可抑制生物膜。进一步研究表明,≥0.8μg/ml的SAN可降低细胞表面疏水性(CSH)并抑制菌丝形成。实时逆转录-聚合酶链反应(RT-PCR)结果表明,白色念珠菌暴露于SAN后,与环磷酸腺苷(cAMP)途径相关的一些黏附及菌丝特异性/必需基因的表达受到抑制,包括ALS1、ALS3、HWP1、SAP2和ECE1。同样,SAN处理后白色念珠菌的内源性cAMP水平下调,添加cAMP可挽救SAN诱导的菌丝形成缺陷。此外,SAN对人脐静脉内皮细胞的毒性相对较低,其50%抑制浓度(IC50)为7.8μg/ml。综上所述,结果表明SAN对白色念珠菌生物膜具有较强活性,且该活性与其通过抑制cAMP途径对黏附和菌丝形成的抑制作用有关。

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