Echinocandin resistance in Candida parapsilosis sensu stricto: Role of alterations in CHS3, FKS1 and Rho gene expression

Abstract

Objectives: 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. Methods: 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. 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. Conclusion: 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.

Keywords

• Candida parapsilosis
• FKS1
• Echinocandin
• CHS3
• Rho