Demonstration of Mutation Development and Virulence Change in Reference Candida Strains Exposed to Caspofungin

Abstract

Purpose: Echinocandin resistance is causing problems in the treatment. FKS gene mutations were detected on the genomes of the resistant Candida strains exposed to echinocandins. The aim of this study was to compare the resistance of reference Candida strains exposed to caspofungin and to investigate whether there was a difference in virulence factors between exposed and non-exposed with caspofungin. Methods: Caspofungin susceptible reference strains, exposed to caspofungin during their incubation in caspofungin containing agar plates at concentrations of 16-0.03 µg/ml. MIC values of caspofungin were determined all strains. FKS gene regions of the caspofungin exposed strains were sequenced in order to reveal the difference between the reference strains. Relationship between caspofungin exposure and virulence properties were investigated in vivo and in vitro methodologies. The in vivo virulence study on the mini-experimental animal model Galleria mellonella (wax moth) was performed. Results: MIC values of the caspofungin exposed strains were found to be increased as one/two fold dilution when compared to the sensitive reference strains. The result of FKS gene sequence no mutation is detected in the reference strains, while a point mutation in caspofungin exposed C. glabrata strains were detected. No significant difference was found in virulence properties of reference strains and caspofungin exposed strains. Conclusions: In conclusion, it was understood that the fact that sensitive strains were exposed to caspofungin even at low concentrations caused an increase in MIC, and that virulence and drug resistance should be evaluated independently.