Mutation in cyp51A and high expression of efflux pump gene of Aspergillus fumigatus induced by propiconazole in liquid medium and soil

• Published in: Environmental pollution (1987) 2020-01, Vol.256, p.113385, Article 113385
• Main Authors: Cao, Duantao, Yao, Shijie, Zhang, Hongchao, Wang, Saige, Jin, Xiangxiang, Lin, Dunli, Fang, Hua, Yu, Yunlong
• Format: Article
• Language: English
• Subjects: Antifungal Agents - toxicity; Aspergillus fumigatus; Aspergillus fumigatus - drug effects; Aspergillus fumigatus - genetics; Cytochrome P-450 Enzyme System - genetics; Drug Resistance, Fungal - drug effects; Drug Resistance, Fungal - genetics; Fungal Proteins - genetics; Fungicide; G138S; Humans; Microbial Sensitivity Tests; Mutation; Resistance; Soil - chemistry; Soil Microbiology; Solutions; Triazole; Triazoles - toxicity
• ISSN: 0269-7491; 1873-6424
• DOI: 10.1016/j.envpol.2019.113385

Triazole resistance in Aspergillus fumigatus is a major cause of clinical inefficacy in the treatment of invasive aspergillosis (IA). The hypothesis that triazole fungicides have driven the development of resistance in A. fumigatus has garnered substantial attention due to the similar structure and global detection of antifungal resistant A. fumigatus (ARAF) isolates in the soil. However, there is little evidence linking the application of triazole fungicides to the emergence of ARAF in the soil. This study was conducted to test if the resistance in A. fumigatus and its associated mutations in cyp51A could be induced by propiconazole in liquid medium and soil. The results indicate that propiconazole can induce resistance by alteration of G138S in cyp51A, and the overexpression of cyp51A, AfuMDR3 and AfuMDR4. G138S in cyp51A was first detected in the soil and associated with resistance. The emergence of the ARAFs in the soil may depends upon the level of propiconazole, and the number of ARAFs in soil treated with propiconazole at 2- and 5-fold dose was much greater than those in soil treated at the recommended dosage. The current data indicate that propiconazole can induce triazole resistance in A. fumigatus and should be applied for agricultural purposes at levels at or below the recommended dosage to avoid the emergence of ARAF in the soil. [Display omitted] •Propiconazole can induce resistance in A. fumigatus to medical triazoles.•G138S in cyp51A was firstly detected in soil.•G138S is associated with the resistance in A. fumigatus to triazole drugs.•Emergence of resistant A. fumigatus in soil may depends upon propiconazole concentration. Propiconazole induces resistance to triazole compounds in A. fumigatus through the mutation of G138S in cyp51A.