Unitat de Microbiologia, Facultat de Medicina i Ciències de la Salut, and Institut d'Investigació Sanitària Pere Virgili (IISPV), Universitat Rovira i Virgili, Reus, Tarragona, Spain.
Med Mycol. 2020 Jan 1;58(1):30-38. doi: 10.1093/mmy/myz014.
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.
光滑念珠菌由于其抗真菌耐药性（主要是对唑类药物）而导致侵袭性念珠菌病难以治疗。本研究的目的是研究 ERG11、CDR1、CDR2 和 SNQ2 基因在一组已知对该药物具有体外和体内敏感性的光滑念珠菌菌株对伏立康唑（VRC）耐药性中的作用。18 株光滑念珠菌临床分离株在体外接触 VRC，通过实时定量聚合酶链反应（q-PCR）定量检测引用基因的表达。此外，扩增和测序 ERG11 基因以检测可能的突变。在 15 株菌株中发现了 10 个同义突变，其中 2 个是首次报道；然而，没有检测到氨基酸变化。在所有测试的菌株中，ERG11 和 CDR1 是表达最多的基因，而 CDR2 和 SNQ2 的表达量适中。我们的结果表明，基因表达与 VRC MIC 不直接相关。此外，在接触 VRC 后，ERG11 和外排泵基因的表达谱并没有一致改变。虽然个体分析没有导致 MIC 和基因表达之间的明确相关性，但我们确实观察到耐药菌株中 ERG11 和 CDR1 的表达增加。有趣的是，考虑到体外和体内结果，这种基因表达的轻微增加与观察到的对 VRC 的耐药性相关。
