Mechanism of berberine-mediated fluconazole-susceptibility enhancement in clinical fluconazole-resistant Candida tropicalis isolates
Mechanism of berberine-mediated fluconazole-susceptibility enhancement in clinical fluconazole-resistant Candida tropicalis isolates
复制标题
小檗碱介导临床氟康唑耐药热带念珠菌氟康唑敏感性增强的机制
DOI：
10.1016/j.biopha.2017.06.106
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发表时间：
2017-09-01
影响因子：
7.5
通讯作者：
Wang, ChangZhong
中科院分区：
文献类型：
--
作者：
Shi, GaoXiang;Shao, Jing;Wang, ChangZhong
背景：热带假丝酵母菌是最常见的非白念珠菌（NACA）之一，具有较高的发病率和死亡率。我们先前证明BBR联合FLC的抗真菌作用可能归因于临床C中活性氧的产生、麦角固醇含量和外排泵水平。方法：采用13株临床分离的热带假丝酵母。通过qRT-PCR检测ERG 11、CDR 1和MDR 1的mRNA表达水平，评价BBR联合FLC在张力状态和生物被膜状态下的抗真菌活性。药敏试验表明，BBR与FLC联用，在低渗状态下FICI范围为0.13-1，在低渗状态下FICI范围为0.25- 1。17株菌在生物被膜状态下的耐药率为1。BBR/FLC单独使用时，ERG 11、CDR 1和MDR 1的mRNA表达较对照组分别上调1.43-2.10倍和1.47-4.42倍。BBR加FLC的组合使用导致2.84-（p < 0.01）和2.39倍（p < 0.05）在ERG 11 mRNA的表达中，2.98-（p < 0.05）和3.06倍与单独使用BBR/FLC相比，CDR 1 mRNA的表达量增加了1.41倍和4.33倍（p < 0.05）。结论：BBR与FLC的协同作用可能与抑制ERG 11和外排泵的mRNA表达有关。(C)2017 Elsevier Masson SAS。All rights reserved.
Background: Candida tropicalis was one of the most common non-albicans Candida (NACA) species creating relatively high morbidity and mortality. We previously demonstrated that the antifungal effect of BBR in combination with FLC might be attributed to reactive oxygen species production, ergosterol content and efflux pump levels in a clinical C. tropicalis isolate.Methods: we employed thirteen clinical C. tropicalis isolates as well as four standard reference strains to evaluate the antifungal activity of BBR in combination with FLC under planktonic and biofilm states by analyzing the mRNA expressions of ERG11, CDR1 and MDR1 by qRT-PCR.Results: The susceptibility tests showed that BBR in combination with FLC produced a FICI range of 0.13-1 under planktonic state and 0.25-1 under biofilm state in the seventeen strains. The mRNA expressions of ERG11, CDR1 and MDR1 were upregulated 1.43-2.10 and 1.47-4.42 fold in the case of BBR/FLC used alone compared with the control. The combined usage of BBR plus FLC resulted in a decrease of 2.84- (p < 0.01) and 2.39-fold (p < 0.05) in the expression of ERG11 mRNA, 2.98- (p < 0.05) and 3.06-fold (p < 0.05) in the expression of CDR1 mRNA, 1.41- and 4.33-fold in the expression of MDR1 mRNA compared with the BBR/FLC used alone.Conclusion: The synergism of BBR with FLC might be relevant with the inhibitions on the mRNA expressions of ERG11 and efflux pumps. (C) 2017 Elsevier Masson SAS. All rights reserved.