Department of Veterinary Medicine, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
Diagnostic Center for Animal Health and Food Safety, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Hokkaido, Japan.
Microbiol Immunol. 2022 Mar;66(3):135-144. doi: 10.1111/1348-0421.12957. Epub 2022 Jan 3.
Aspergillus fumigatus, a ubiquitous pathogen, causes aspergillosis in humans, especially in immunodeficient patients. Azoles are frontline antifungal drugs for treating aspergillosis. The recent global emergence of azole resistance in A. fumigatus has become a serious problem worldwide. It has arisen through two routes: long-term azole medical therapy, called the patient route, and the use of azole fungicides in its habitats especially for agricultural activities, called the environmental route. Resistant strains developed through the latter route show cross-resistance to medical azoles because of the identical molecular target Cyp51A between azole compounds used for medical treatment and agricultural disease control. In azole-resistant strains arising through the environmental route, A. fumigatus is observed frequently to possess mutations in the cyp51A gene linked to tandem repeats in the promoter region such as TR /L98H and TR /Y121F/T289A. The results of microsatellite genotyping analyses of resistant A. fumigatus strains have suggested a transboundary spread of this microorganism in many countries. Diverse actors are involved in the global highway of transmission. Therefore, the matter must be addressed as a "One Health" issue. This review presents a background of azole resistance in A. fumigatus and introduces newly discovered difficulties generated as this pathogen spreads worldwide.
烟曲霉是一种无处不在的病原体，可导致人类曲霉病，尤其是免疫功能低下的患者。唑类药物是治疗曲霉病的一线抗真菌药物。最近，烟曲霉对唑类药物的全球耐药性的出现已成为全球范围内的一个严重问题。它主要通过两种途径产生：长期唑类药物治疗，称为患者途径，以及在其栖息地（特别是用于农业活动）中使用唑类杀真菌剂，称为环境途径。通过后者途径产生的耐药菌株由于用于治疗和农业疾病控制的唑类化合物具有相同的分子靶标 Cyp51A，因此对医学唑类药物表现出交叉耐药性。在通过环境途径产生的唑类耐药菌株中，烟曲霉经常观察到 cyp51A 基因发生与启动子区域中的串联重复（如 TR/L98H 和 TR/Y121F/T289A）相关的突变。对耐药烟曲霉菌株进行的微卫星基因分型分析的结果表明，这种微生物在许多国家发生了跨界传播。不同的行为体都参与了这种微生物的全球传播。因此，必须将其视为一个“同一健康”问题来解决。本文介绍了烟曲霉对唑类药物耐药性的背景，并介绍了这种病原体在全球传播过程中产生的新发现的困难。
