Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Invasive Fungi Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran; Department of Medical Mycology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran.
J Glob Antimicrob Resist. 2020 Sep;22:685-688. doi: 10.1016/j.jgar.2020.06.025. Epub 2020 Jul 9.
The rate of resistance of Candida parapsilosis to echinocandins remains unexplored in Iran. The main aims of this study were to investigate the susceptibility patterns and possible mechanisms of echinocandin resistance in echinocandin-resistant clinical C. parapsilosis isolates in Iran.
A total of 105 isolates of C. parapsilosis sensu stricto underwent antifungal susceptibility testing to echinocandins by the broth microdilution reference method. Sequences of the CpERG3 and CpFKS1 genes were analysed using MEGA6 software, and alterations in CHS3, FKS1 and Rho gene expression were evaluated by quantitative reverse transcription (RT-qPCR). REST® software was used to analyse the results.
The rate of echinocandin cross-resistance was 2.9% (3/105). No substitutions were detected in Fks1p except for the naturally occurring P660A amino acid substitution observed in isolates both with high and low minimum inhibitory concentrations (MICs). Moreover, the G111R amino acid substitution was not found in Erg3p. Following echinocandin exposure, expression of Rho and FKS1 genes was significantly increased in resistant isolates, whilst the CHS3 gene showed no change.
Alterations in the expression of some key genes may be responsible for echinocandin resistance among C. parapsilosis isolates. Understanding the mechanisms responsible for drug resistance in C. parapsilosis is not only crucial for the development of new antifungals but is also important in choosing appropriate antifungals for patient treatment at the earliest stage.
棘白菌素类耐药的近平滑念珠菌在伊朗的耐药率尚不清楚。本研究的主要目的是调查伊朗棘白菌素耐药临床近平滑念珠菌分离株的药敏模式和棘白菌素耐药的可能机制。
采用肉汤微量稀释法对 105 株严格意义上的近平滑念珠菌进行抗真菌药敏试验。使用 MEGA6 软件分析 CpERG3 和 CpFKS1 基因序列，并通过定量逆转录聚合酶链反应（RT-qPCR）评估 CHS3、FKS1 和 Rho 基因表达的改变。使用 REST®软件分析结果。
棘白菌素交叉耐药率为 2.9%（3/105）。除了在高和低最小抑菌浓度（MIC）的分离株中观察到的天然存在的 P660A 氨基酸取代外，Fks1p 中未检测到取代。此外，在 Erg3p 中未发现 G111R 氨基酸取代。在棘白菌素暴露后，耐药分离株中 Rho 和 FKS1 基因的表达显著增加，而 CHS3 基因没有变化。
一些关键基因表达的改变可能是导致近平滑念珠菌分离株对棘白菌素耐药的原因。了解近平滑念珠菌耐药的机制不仅对开发新的抗真菌药物至关重要，而且对于在早期阶段为患者治疗选择合适的抗真菌药物也很重要。
