Changes in Genotype and Fluconazole Susceptibility of Isolates from Patients with Candida glabrata in Tunisia

Abstract Candida glabrata has emerged as an opportunistic pathogen of considerable importance in invasive and superficial infections. Aims To analyze the development of fluconazole resistance in patients under treatment through epidemiological survey in our hospital. Patients and methods Twenty two patients (89 clinical strains) were collected. Molecular typing of isolates was performed by polymorphic markers. Analysis of gene expression was realized by reverse transcriptase-real time polymerase chain reactions (RT-qPCR). Results Genetic analysis showed that 63% persists with apparently unchanged strains (n = 14). Among them, four showed fluconazole resistance development. A strain replacement was observed in 6 patients and two patients selected more resistant isolates during the course of treatment. An analysis of Candida glabrata cerebellar degeneration-related protein 1 (CgCDR1), Candida glabrata cerebellar degeneration-related protein 2 (CgCDR2) and Candida glabrata sterol 14 alpha-demetylase Erg 11 (CgERG11) expression revealed an over-expression in 10 resistant isolates. Conclusion This study demonstrated that C. glabrata strain undergo frequent changes in vivo . The increase in CgCDR1 and CgCDR2 expression was the most mechanism associated with fluconazole resistance.