Anti-microbial and anti-biofilm activities of combined chelerythrine-sanguinarine and mode of action against Candida albicans and Cryptococcus neoformans in vitro
Anti-microbial and anti-biofilm activities of combined chelerythrine-sanguinarine and mode of action against Candida albicans and Cryptococcus neoformans in vitro
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DOI：
10.1016/j.colsurfb.2020.111003
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发表时间：
2020-07-01
影响因子：
5.8
通讯作者：
Wang, Ting
中科院分区：
文献类型：
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作者：
Qian, Weidong;Yang, Min;Wang, Ting
随着真菌感染的日益流行以及耐药性的出现，迫切需要探索新的有效的抗真菌药物。血根碱和车腥草碱是具有抗真菌活性的生物碱。然而，这些药物1:1的混合物对白色念珠菌和新型隐球菌的影响在很大程度上仍未被探索。本研究的目的是评价车车苋-血根碱联合抗白色念珠菌和新生念珠菌的体外抗真菌和抗生物膜效果。chelerythrin -sanguinarine联合使用时，最低抑制浓度（mic）分别为2 μ g/mL和16 μ g/mL时，可抑制白色念珠菌和新生念珠菌的生长；最低生物膜抑制浓度为1 μ g/mL和8 μ g/mL时，可有效抑制病原菌的粘附和生物膜的形成。值得注意的是，在8 μ g/mL和128 μ g/mL的浓度下，该混合物可显著根除成熟的白色念珠菌和新生念珠菌生物膜。特别是，混合物被发现破坏细胞膜完整性，增强抗生素对真菌细胞的渗透，表明其抗真菌的作用模式。因此，chelerythrine-sanguinarine联合应用有望成为一种潜在的抗真菌和抗生物膜药物，用于治疗由白色念珠菌和新生念珠菌引起的严重感染。
The increasing prevalence of fungal infections coupled with emerging drug resistance has stimulated an urgent need to explore new and effective antifungal agents. Sanguinarine and chelerythrine constitute alkaloids that have exhibited antifungal activities. However, the effects of a 1:1 mixture of these agents against Candida albicans and Cryptococcus neoformans have remained largely unexplored. The purpose of this study was to assess the anti-fungal and anti-biofilm efficacy of combined chelerythrine-sanguinarine against C. albicans and C. neoformans in vitro. Combined chelerythrine-sanguinarine inhibited C. albicans and C. neoformans growth with minimum inhibitory concentrations (MICs) of 2 and 16 mu g/mL, respectively, and effectively inhibited adhesion and biofilm formation of these pathogens at minimum biofilm inhibitory concentrations of 1 and 8 mu g/mL. Notably, the mixture significantly eradicated mature C. albicans and C. neoformans biofilms at 8 and 128 mu g/mL, respectively. In particular, the mixture was found to disrupt cell membrane integrity and enhance penetration of antibiotics into fungal cells, suggesting its antifungal mode of action. Hence, combined chelerythrine-sanguinarine shows promise as a potential anti-fungal and anti-biofilm agent for the management of serious infections caused by C. albicans and C. neoformans.