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.. Candida glabrata

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 q-PCR. In addition, the ERG11 gene was amplified and sequenced to detect possible mutations, thirteen mutations were found in fifteen strains, of which six were reported for first time, but no aminoacid changes were observed in any of the strains. ERG11 and CDR1 were the most expressed genes in all strains tested, while the expression of CDR2 and SNQ2 was modest, however did not correlate with the MIC scale in any case. 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 slightly increase in such gene expression correlates with the observed resistance to VRC.

光滑念珠菌（Candida glabrata）可引发难治性侵袭性念珠菌病，原因在于其对包括唑类在内的抗真菌药物存在耐药性。本研究旨在探究ERG11、CDR1、CDR2及SNQ2基因，在一组已知伏立康唑（voriconazole，VRC）体外与体内敏感性的光滑念珠菌菌株中，对该药物耐药性的调控作用。本研究纳入18株光滑念珠菌临床分离株，体外给予伏立康唑处理后，采用实时定量聚合酶链反应（real-time q-PCR）对上述基因的表达水平进行定量检测。此外，对ERG11基因进行扩增与测序以筛查潜在突变：共在15株菌株中检出13处突变，其中6处为首次报道，但未在任何菌株中观察到氨基酸序列改变。在所有受试菌株中，ERG11与CDR1的表达水平最高，而CDR2与SNQ2的表达则相对微弱；不过无论何种情况，其表达水平均与最低抑菌浓度（MIC）值无相关性。此外，经伏立康唑诱导后，ERG11与外排泵基因的表达谱未出现一致性变化。尽管单因素分析未能明确最低抑菌浓度与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与CDR1的表达水平有所升高。值得关注的是，综合体外与体内实验结果，这类基因表达的轻度上调与实验观察到的伏立康唑耐药性存在相关性。