The study on the relationship between ERG11 gene and azole-resistant isolates of Candida tropicalis

Abstract

Abstract:

Objective To investigate the mutation and expression of ERG11 gene in clinical azole-resistant Candida tropicalis isolates. Methods The clinical Candida tropicalis isolates were collected and identified, then antifungal susceptibility tests to fluconazole, voriconazole and itraconazole were performed. ERG11 which was the gene coding antifungal drug target enzyme of cytochrome P450 lanosterol 14a-demethylase, was quantified by real-time RT-PCR and sequenced. The sequencing results were compared with the known standard sequence (M23673) in GenBank. Results There were 92 clinical Candida tropicalis isolates were obtained, of which 29 were resistant to at least one of the above three azole antifungals. Two missense mutations (S154F,Y132F) and five synonymous mutations were found in 40 clinical isolates, including 29 azole-resistant isolates and 11 azole-susceptible isolates. It is worth noting that the two missense mutations were existed in 24 of 29 azole-resistant isolates, however, no missense mutations were found in azole-susceptible isolates. The results of real-time PCR showed that the expression of ERG11 gene in azole-resistant clinical isolates was significantly higher than that in azole-susceptible isolates, and 16 isolates resistant to all three of the azole antifungals had a higher level of ERG11 gene expression than 13 isolates that were only resistant to one or two azole antifungals. Conclusions Azole resistance of clinical Candida tropicalis isolates is associated with the mutations and overexpression of ERG11 gene, and the resistance mechanism of Candida tropicalis to azole antifungals needs further study.

Key words: Candida tropicalis, azole resistance, ERG11 gene

CLC Number:

R379.4

WANG Ying, XIANG Ming-jie, LIU Jin-yan, YE Shu-lai, ZHOU xin. The study on the relationship between ERG11 gene and azole-resistant isolates of Candida tropicalis[J]. Chinese Journal of Mycology, 2019, 14(6): 332-337.

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