ena-STUDY-URV-26-01-2019-20:13:43:181-1308
Candida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11, CDR1, CDR2 and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug.
Candida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11, CDR1, CDR2 and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug.  Eighteen clinical isolates of C. glabrata were exposed in vitro to VRC and the expression of the cited genes was quantified by real time q-PCR. In addition, the ERG11 gene was amplified and sequenced to detect possible mutations, thirteen mutations were found in fifteen strains, of which six were reported for first time, but no aminoacid changes were observed in any of the strains. ERG11 and CDR1 were the most expressed genes in all strains tested, while the expression of CDR2 and SNQ2 was modest, however did not correlate with the MIC scale in any case. In addition, the expression profiles of ERG11 and efflux pump genes did not change consistently after exposure to VRC. Although individual analysis did not result in a clear correlation between MIC and gene expression, we did observe an increase in ERG11 and CDR1 expression in resistant strains. It is of interest that considering both in vitro and in vivo results, the slightly increase in such gene expression correlates with the observed resistance to VRC.
Candida glabrata causes difficult to treat invasive candidiasis due to its antifungal resistance, mainly to azoles. The aim of the present work was to study the role of the genes ERG11, CDR1, CDR2 and SNQ2 on the resistance to voriconazole (VRC) in a set of C. glabrata strains with known in vitro and in vivo susceptibility to this drug.  Eighteen clinical isolates of C. glabrata were exposed in vitro to VRC and the expression of the cited genes was quantified by real time q-PCR. In addition, the ERG11 gene was amplified and sequenced to detect possible mutations, thirteen mutations were found in fifteen strains, of which six were reported for first time, but no aminoacid changes were observed in any of the strains. ERG11 and CDR1 were the most expressed genes in all strains tested, while the expression of CDR2 and SNQ2 was modest, however did not correlate with the MIC scale in any case. In addition, the expression profiles of ERG11 and efflux pump genes did not change consistently after exposure to VRC. Although individual analysis did not result in a clear correlation between MIC and gene expression, we did observe an increase in ERG11 and CDR1 expression in resistant strains. It is of interest that considering both in vitro and in vivo results, the slightly increase in such gene expression correlates with the observed resistance to VRC.