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苦参碱可降低白念珠菌耐氟康唑株的酵母-菌丝过渡和耐药性。

Matrine reduces yeast-to-hypha transition and resistance of a fluconazole-resistant strain of Candida albicans.

机构信息

Laboratory of Microbiology and Immunology, School of Chinese and Western Integrative Medicine, Anhui University of Chinese Medicine, Hefei, China.

出版信息

J Appl Microbiol. 2014 Sep;117(3):618-26. doi: 10.1111/jam.12555. Epub 2014 Jun 26.

Abstract

AIMS

To evaluate the potential effect of matrine on reducing the growth of hypha and lowering the resistance of a fluconazole-resistant colony of Candida albicans.

METHODS AND RESULTS

Candida albicans SC5314 and a fluconazole-resistant C. albicans 215 were used. As for C. albicans SC5314, minimal inhibitory concentration (MIC(80)) and effective concentration (EC(50)) were determined, 1 mg ml(-1) matrine could inhibit nearly 80% of planktonic growth by inverted microscope, 2 mg ml(-1) matrine suppressed 50% of metabolic activity of biofilm by XTT assay, vanishing hypha could be observed on spider agar containing 2 mg ml(-1) matrine, the expressions of three hypha-related genes, namely ALS 3, SUN 41 and PBS 2, were suppressed by 29, 45 and 61% by 2 mg ml(-1) matrine. Also, matrine could lower the resistance of C. albicans 215, in either the free-floating form or the biofilm phenotype.

CONCLUSIONS

Matrine had favourable antifungal potential and might be able to reverse the fluconazole resistance of clinical isolates at relatively high concentration. The anti-candidal performance of matrine could be tightly associated with yeast-to-hypha transition proved by spider agar test and qRT-PCR.

SIGNIFICANCE AND IMPACT OF STUDY

More efforts are needed to find new antifungal agents. Matrine could be a potential candidate to fight against Candida-related infections by regulating yeast-to-hypha transition.

摘要

目的

评估苦参碱降低白色念珠菌丝状生长和降低氟康唑耐药菌落抗性的潜在作用。

方法与结果

使用白色念珠菌 SC5314 和氟康唑耐药白色念珠菌 215。对于白色念珠菌 SC5314,测定最小抑菌浓度(MIC(80))和有效浓度(EC(50)),苦参碱 1mg/ml 可通过倒置显微镜抑制近 80%的浮游生长,苦参碱 2mg/ml 可通过 XTT 测定抑制生物膜 50%的代谢活性,在含有 2mg/ml 苦参碱的蜘蛛琼脂上可观察到菌丝消失,苦参碱 2mg/ml 可分别抑制 ALS3、SUN41 和 PBS2 这三个菌丝相关基因的表达 29%、45%和 61%。此外,苦参碱可以降低游离形式或生物膜表型的白色念珠菌 215 的耐药性。

结论

苦参碱具有良好的抗真菌潜力,可能能够在相对较高的浓度下逆转临床分离株的氟康唑耐药性。苦参碱的抗白色念珠菌性能可能与通过蜘蛛琼脂试验和 qRT-PCR 证明的酵母向菌丝过渡密切相关。

研究的意义和影响

需要更多的努力来寻找新的抗真菌药物。苦参碱可以通过调节酵母向菌丝过渡成为一种潜在的抗念珠菌感染候选药物。

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