Drug susceptibility profile of Candida glabrata clinical isolates from Iran and genetic resistant mechanisms to caspofungin

Abstract

Background: Candida glabrata is a yeast that can cause hazardous fungal infections with high mortality and drug resistance.

Aims: The aim of this study was to determine the profile of drug susceptibility in clinical isolates of C. glabrata and review the resistance mechanisms to caspofungin.

Methods: A total of 50 C. glabrata clinical isolates from Iran were tested for in vitro susceptibilities to amphotericin B, caspofungin, fluconazole and voriconazole. To investigate the mechanism of resistance to caspofungin, hotspot areas of FKS1 and FKS2 genes were sequenced and gene expression profile was evaluated.

Results: All the isolates were susceptible to amphotericin B and caspofungin. Fluconazole resistance was exhibited in four isolates. In addition, only one isolate was resistant to voriconazole. FKS2 with 12 point mutations showed more mutations compared to FKS1 that had only two mutations. All substitutions were synonymous. FKS genes were expressed at comparable levels (no statistical significance) in caspofungin-treated and non-treated cultures.

Conclusions: The silent mutations in the hotspot areas of FKS genes and inconsiderable changes in gene expression were not associated with increased MIC (0.25μg/ml). Other mechanisms of resistance which include mutations outside the hotspot area of FKS genes could be involved in a slight increase of MIC, and they should be identified through complete FKS gene sequencing.

Keywords: Candida glabrata; Candidiasis; Caspofungin; Caspofungina; Drug susceptibility; Echinocandins; Equinocandinas; Sensibilidad antifúngica.