Candida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11, CDR1, CDR2, and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug. Eighteen clinical isolates of C. glabrata were exposed in vitro to VRC, and the expression of the cited genes was quantified by real time quantitative polymerase chain reaction (q-PCR). In addition, the ERG11 gene was amplified and sequenced to detect possible mutations. Ten synonymous mutations were found in 15 strains, two of them being reported for the first time; however, no amino acid changes were detected. ERG11 and CDR1 were the most expressed genes in all the strains tested, while the expression of CDR2 and SNQ2 was modest. Our results show that gene expression does not directly correlate with the VRC MIC. In addition, the expression profiles of ERG11 and efflux pump genes did not change consistently after exposure to VRC. Although individual analysis did not result in a clear correlation between MIC and gene expression, we did observe an increase in ERG11 and CDR1 expression in resistant strains. It is of interest that considering both in vitro and in vivo results, the slight increase in such gene expression correlates with the observed resistance to VRC.

中文翻译：

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ERG11和外排泵基因CDR1，CDR2和SNQ2在伏立康唑易感和耐药的光滑念珠菌菌株中的表达。

光滑念珠菌由于其主要是对唑类的抗真菌性而导致难以治疗侵袭性念珠菌病。本工作的目的是研究基因ERG11，CDR1，CDR2和SNQ2在一组已知体外和体内对该药物易感性的光滑小隐球菌菌株中对伏立康唑（VRC）的抗性的作用。将十八个光滑念珠菌临床分离株体外暴露于VRC，并通过实时定量聚合酶链反应（q-PCR）定量引用基因的表达。此外，ERG11基因被扩增并测序以检测可能的突变。在15个菌株中发现了10个同义突变，其中两个是首次报道。但是，未检测到氨基酸变化。在所有测试的菌株中，ERG11和CDR1是表达最多的基因，CDR2和SNQ2的表达适中。我们的结果表明基因表达与VRC MIC不直接相关。此外，ERG11和外排泵基因的表达谱在暴露于VRC后并没有一致地改变。尽管个别分析没有导致MIC和基因表达之间的明确关联，但我们确实观察到耐药菌株中ERG11和CDR1表达的增加。令人感兴趣的是，考虑到体外和体内结果，此类基因表达的轻微增加与观察到的对VRC的抗性相关。尽管单独的分析没有导致MIC和基因表达之间的明确关联，但我们确实观察到耐药菌株中ERG11和CDR1表达的增加。令人感兴趣的是，考虑到体外和体内结果，此类基因表达的轻微增加与观察到的对VRC的抗性相关。尽管单独的分析没有导致MIC和基因表达之间的明确关联，但我们确实观察到耐药菌株中ERG11和CDR1表达的增加。令人感兴趣的是，考虑到体外和体内结果，此类基因表达的轻微增加与观察到的对VRC的抗性相关。