The Role of UPC2 Gene in Azole-Resistant Candida tropicalis.

Abstract

Azole resistance of Candida tropicalis has, in recent years, become a serious issue in hospitals; however, there is limited knowledge of the mechanisms underlying this resistance. We have previously demonstrated that ERG11 plays a vital role in azole resistance in C. tropicalis. Here, we describe the expression and sequence variation of UPC2, which encodes a transcription factor of ERG11. Quantitative real-time RT-PCR showed that 31 azole-resistant C. tropicalis strains significantly overexpressed UPC2. Those isolates resistant to all three azole antifungals upregulated UPC2 expression to a greater degree than those resistant to only fluconazole or itraconazole. The UPC2 promoter contains mutations -118T-G and -155G-A in azole-resistant strains of C. tropicalis. Meanwhile, the mutation G392E was also detected twice in UPC2 gene in azole-resistant C. tropicalis and was demonstrated to mediate azole antifungal susceptibility by using Saccharomyces cerevisiae as an expression host, particularly for fluconazole and itraconazole.