Upregulation of the ERG11 gene in Candida krusei by azoles

BACKGROUND AND THE PURPOSE OF THE STUDY: Candida species are the agents of local and systemic opportunistic infections and have become a major cause of morbidity and mortality in the last few decades. Azole resistance in Candida krusei (C. krusei) species appears to be the result of gene alterations in relation to the ergosterol biosynthesis pathway, as well as efflux pumps. The main objective of this study was to examine the RNA expression of ERG11 in C. krusei which had been identified to be resistance to azoles. METHODS: The ERG11 mRNA expression was investigated in four Iranian clinical isolates of C. krusei, which were resistant to fluconazole and itraconazole by a semiquantitative RT-PCR. Results: The mRNA expression levels were observed in all four isolates by this technique. Furthermore, it was found that ERG11 expression levels vary among four representative isolates of C. krusei. Although DNA sequencing revealed no significant genetic alteration in the ERG11 gene, one heterozygous polymorphism was observed in two isolates, but not in others. This polymorphism was found in the third base of codon 313 for Thr (ACT>ACC). MAJOR CONCLUSION: Even though such a polymorphism creates a new Ear1 restriction site, no significant effect was found on the resistance of C. krusei to azoles. Results of this investigation are consistent with previous studies and may provide further evidence for the genetic heterogeneity and complexity of the ergosterol biosynthetic pathway or efflux pumps.