Elevated MIC Values of Imidazole Drugs against Aspergillus fumigatus Isolates with TR34/L98H/S297T/F495I Mutation
Elevated MIC Values of Imidazole Drugs against Aspergillus fumigatus Isolates with TR34/L98H/S297T/F495I Mutation
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DOI：
10.1128/aac.01549-17
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发表时间：
2018-05-01
影响因子：
4.9
通讯作者：
Han, Li
中科院分区：
文献类型：
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作者：
Chen, Yong;Li, Zongwei;Han, Li
在农业上使用唑类杀菌剂被认为是烟曲霉产生唑类抗药性的主要原因之一。虽然咪唑类杀菌剂在农业中被广泛使用，但与烟曲霉的抗药性无关。本研究表明，咪唑类药物对TR34/L98H/S297T/F495I突变烟曲霉菌的MIC值升高，但对TR34/L98H突变菌株的MIC值无明显影响。对来自20个国家和地区的580株烟曲霉菌的短串联重复序列分型分析表明，中国的TR34/L98H/S297T/F495I菌株与荷兰和丹麦的大多数唑类耐药菌株和具有相同突变的菌株构成的优势主要分支存在遗传差异。类固醇14α-脱甲基酶序列的比对表明，烟曲霉的F495I与指状青霉菌的F506I和圆锥菌的F489L同源，这两个基因已被报道与咪唑耐药性有关。体外药敏试验进一步证实了F495I突变与咪唑耐药的关系。综上所述，本研究提示咪唑类杀菌剂的环境使用可能为烟曲霉产生唑类耐药性提供了选择压力。
The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Aspergillus fumigatus. Though widely used in agriculture, imidazole fungicides have not been linked to resistance in A. fumigatus. This study showed that elevated MIC values of imidazole drugs were observed against A. fumigatus isolates with TR34/L98H/S297T/F495I mutation, but not among isolates with TR34/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 A. fumigatus isolates from 20 countries suggested that the majority of TR34/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14 alpha-demethylase sequences suggested that F495I in A. fumigatus was orthologous to F506I in Penicillium digitatum and F489L in Pyrenophora teres, which have been reported to be associated with imidazole resistance. In vitro antifungal susceptibility testing of different recombinants with cyp51A mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in A. fumigatus.