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刺楸皂苷A的抗念珠菌活性:对其增殖、细胞形态及关键毒力属性的影响

Anticandidal Activity of Kalopanaxsaponin A: Effect on Proliferation, Cell Morphology, and Key Virulence Attributes of .

作者信息

Li Ying, Shan Mingzhu, Yan Mingju, Yao Huankai, Wang Yuechen, Gu Bing, Zhu Zuobin, Li Hongchun

机构信息

School of Medical Technology, Xuzhou Medical University, Xuzhou, China.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, School of Clinical Pharmacy, Xuzhou Medical University, Xuzhou, China.

出版信息

Front Microbiol. 2019 Dec 3;10:2844. doi: 10.3389/fmicb.2019.02844. eCollection 2019.

Abstract

BACKGROUND

The pathogenicity of is attributed to various virulence factors including adhesion to the surface of epithelial cells or mucosa, germ tube formation, hyphal morphogenesis, development of drug resistant biofilms, and so on. The objective of this study was to investigate the effects of Kalopanaxsaponin A (KPA) on the virulence of .

METHODS

The effect of KPA on the virulence of was characterized by an XTT reduction assay and fluorescent microscopic observation. The action mechanism was further explored using GC/MS system and BioTek Synergy2 spectrofluorophotometry. The cytotoxicity and therapeutic effect of KPA were evaluated by the - infection model .

RESULTS

The minimum inhibitory concentration (MIC) of KPA was 8∼16 μg/mL for various genotypes of . The compound was identified as having remarkable effect on the adhesion, morphological transition and biofilm formation of . The results of fluorescent microscopy and GC/MS system suggested that KPA could promote the secretion of farnesol by regulating the expression of Dpp3 and decrease the intracellular cAMP level, which together inhibited morphological transition and biofilm formation. Notably, KPA showed low toxicity and a low possibility of developing resistance.

CONCLUSION

Our results demonstrated that KPA had remarkable efficacy against pathogenicity, suggesting that it could be a potential option for the clinical treatment of candidiasis.

摘要

背景

的致病性归因于多种毒力因子,包括对上皮细胞或粘膜表面的粘附、芽管形成、菌丝形态发生、耐药生物膜的形成等。本研究的目的是探讨刺五加皂苷A(KPA)对的毒力的影响。

方法

通过XTT还原试验和荧光显微镜观察来表征KPA对的毒力的影响。使用GC/MS系统和BioTek Synergy2荧光分光光度计进一步探索作用机制。通过感染模型评估KPA的细胞毒性和治疗效果。

结果

KPA对不同基因型的的最低抑菌浓度(MIC)为8∼16μg/mL。该化合物被确定对的粘附、形态转变和生物膜形成有显著影响。荧光显微镜和GC/MS系统的结果表明KPA可通过调节Dpp3的表达促进法尼醇的分泌并降低细胞内cAMP水平,从而共同抑制形态转变和生物膜形成。值得注意的是,KPA显示出低毒性和低耐药可能性。

结论

我们的结果表明KPA对致病性具有显著疗效,表明它可能是念珠菌病临床治疗的潜在选择。

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