Arai Teppei, Majima Hidetaka, Maruguchi Naoto, Ban Sayaka, Yaguchi Takashi, Watanabe Akira
Division of Clinical Research, Medical Mycology Research Center, Chiba University.
Management Unit of Microbiological Resources, Medical Mycology Research Center, Chiba University.
Med Mycol J. 2025;66(3):131-137. doi: 10.3314/mmj.25-00014.
In recent years, increased azole-resistant Aspergillus fumigatus (ARAf) isolation has been reported worldwide, and it poses a major threat. The main cause of resistance originates from mutations in the cyp51A gene, which encodes 14α-demethylase. Among the clinical isolates we received before 2024, a designated point mutation in their Cyp51A protein was the main mechanism of resistance for ARAf. However, from 2024, ARAf with tandem repeats (TRs) of 34 or 46 base-pairs in the promoter region of the cyp51A gene and amino acid substitutions in the coding region (TR-ARAf), which have been widely reported overseas but seldom found in Japan, has become isolated more frequently. Among the 111 A. fumigatus strains referred to our institution in 2024, ten strains were ARAf, of which four were TR-ARAf. Our study indicates that the prevalence of TR-ARAf in Japan is potentially on the rise, possibly posing a serious threat to public health. This trend might have serious implications for the management of aspergillosis in the country in the near future.
近年来，全球范围内耐唑类烟曲霉（ARAf）的分离率不断上升，构成了重大威胁。耐药的主要原因源于编码14α-脱甲基酶的cyp51A基因突变。在我们2024年之前收到的临床分离株中，其Cyp51A蛋白的特定点突变是ARAf耐药的主要机制。然而，自2024年起，cyp51A基因启动子区域存在34或46个碱基对串联重复序列（TRs）且编码区存在氨基酸替换的ARAf（TR-ARAf）在海外已被广泛报道，但在日本很少发现，其分离频率却越来越高。在2024年提交至我们机构的111株烟曲霉菌株中，有10株为ARAf，其中4株为TR-ARAf。我们的研究表明，TR-ARAf在日本的流行率可能正在上升，可能对公众健康构成严重威胁。这一趋势可能在不久的将来对该国曲霉病的管理产生严重影响。
