التفاصيل البيبلوغرافية
العنوان: |
N-Butylphthalide Potentiates the Effect of Fluconazole Against Drug-Resistant Candida glabrata and Candida tropicalis. Evidence for Its Mechanism of Action. |
المؤلفون: |
Liu, Yixin, Ren, Feifei, Li, Shan, Li, Xiangchen, Shi, Dongyan, Zhang, Zhiqing |
المصدر: |
Infection & Drug Resistance; May2024, Vol. 17, p2017-2029, 13p |
مصطلحات موضوعية: |
CANDIDA tropicalis, ANTIFUNGAL agents, CANDIDA, CYTOCHROME oxidase, FLUCONAZOLE, GENE expression, DRUG target |
مستخلص: |
To define the antifungal activity of n-butylphthalide alone or in combination with fluconazole in Candida glabrata and Candida tropicalis. Methods: The antifungal activity of n-butylphthalide alone and in combination with fluconazole was investigated by the classical broth microdilution method and the time-killing curve method. The QRT-PCR method was used to determine gene expressions changes of mitochondrial respiratory chain enzymes, drug efflux pumps and drug target enzymes in Candida glabrata and Candida tropicalis after n-butylphthalide treatment. Results: The MIC values of n-butylphthalide against Candida glabrata and Candida tropicalis ranged from 16 to 64 μg·mL-1. The FICI value of the combination of n-butylphthalide and fluconazole against drug-resistant Candida glabrata and Candida tropicalis ranged from 0.5001 to 0.5315 with partial synergism. Time-killing curves showed that 256 μg·mL-1 n-butylphthalide significantly inhibited the growth of drug-resistant colonies of Candida glabrata and Candida tropicalis, and 128 μg·mL-1 n-butylphthalide combined with 1 μg·mL-1 fluconazole had an additive effect. N-butylphthalide could alter the expression of mitochondrial respiratory chain enzymes COX1, COX2, COX3, and CYTB genes in Candida glabrata and Candida tropicalis (P< 0.05) and downregulate the expression of the drug efflux pump genes CDR1 and CDR2 in drug-resistant Candida glabrata to 3.36% and 3.65%, respectively (P< 0.001), but did not affect the drug target enzyme ERG11 in drug-resistant Candida tropicalis. Conclusion: N-butylphthalide had antifungal activity against Candida glabrata and Candida tropicalis. N-butylphthalide improved the activity of fluconazole against drug-resistant Candida glabrata by affecting the expression of mitochondrial respiratory chain enzyme genes and reversing the high expression of drug efflux pump genes CDR1 and CDR2. [ABSTRACT FROM AUTHOR] |
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قاعدة البيانات: |
Complementary Index |