The features and mechanisms of Candida tropicalis resistance in vitro induced by different azoles

Abstract

Abstract:

Objective To compare the features of different azoles in vitro induction of azole resistance in Candida tropicalis, and related resistant mechanisms.Methods A clinical azole-susceptible isolate was consecutively subcultured in liquid medium containing 16 μg/mL of fluconazole, 2 μg/mL of voriconazole or 1 μg/mL of posaconazole, respectively, for 50 generations. Antifungal susceptibility testing was performed by colorimetric broth microdilution method. The azoles target gene, ERG11, of the 50^th generation isolates were amplified and sequenced. In addition, the expression level of ERG11, and efflux pump-encoding gene MDR1, CDR1, as well as cytochrome b-encoding gene CYTb, were determined by real-time quantitative PCR.Results Azole resistance was emerged very fast when under in vitro exposure to fluconazole or voriconazole, whilst the isolates induced by posaconazole remained susceptible. However, the resistance features of isolates induced by fluconazole and voriconazole were different. The MICs of isolates induced by fluconazole were gradually increased, while MICs of isolates induced by voriconazole had a jump rise. By resistant mechanism study, a G/G1390G/A heterozygous mutation being responsible for azole resistance was detected in ERG11 gene of voriconazole-induced isolate. The real-time PCR results showed that, only the expression of CDR1 gene in fluconazole-induced isolates increased significantly.Conclusions Azole resistance amongst C.tropicalis isolates emerged rapidly under in vitro exposure to fluconazole or voriconazole, but the resistant features and mechanisms were different.

Key words: Candida tropicalis, resistant mechanism, induction of azole resistance

CLC Number:

R379.4

FAN Xin, HUANG Jing-jing, HOU Xin, XIAO Meng, ZHANG Li, XU Ying-chun. The features and mechanisms of Candida tropicalis resistance in vitro induced by different azoles[J]. Chinese Journal of Mycology, 2018, 13(4): 197-200.

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