Abstract：
Aspergillus fumigatus is a ubiquitous filamentous fungus commonly found in the environment. It is also an opportunistic human pathogen known to cause a range of respiratory infections, such as invasive aspergillosis, particularly in immunocompromised individuals. Azole antifungal agents are widely used for the treatment and prophylaxis of Aspergillus infections due to their efficacy and tolerability. However, the emergence of azole resistance in A. fumigatus has become a major concern in recent years due to their association with increased treatment failures and mortality rates. The development of azole resistance in A. fumigatus can occur through both acquired and intrinsic mechanisms. Acquired resistance typically arises from mutations in the target enzyme, lanosterol 14-α-demethylase (Cyp51A), reduces the affinity of azole antifungal agents for the enzyme, rendering them less effective, while intrinsic resistance refers to a natural resistance of certain A. fumigatus isolates to azole antifungals due to inherent genetic characteristics. The current review aims to provide a comprehensive overview of azole antifungal resistance in A. fumigatus, discusses underlying resistance mechanisms, including alterations in the target enzyme, Cyp51A, and the involvement of efflux pumps in drug efflux. Impact of azole fungicide uses in the environment and the spread of resistant strains is also explored.
摘要：
烟曲霉是一种普遍存在于环境中的丝状真菌。它也是一种机会性人类病原体，已知会导致一系列呼吸道感染，比如侵袭性曲霉病,特别是在免疫受损的个体中。唑类抗真菌剂由于其功效和耐受性而广泛用于治疗和预防曲霉属感染。然而,近年来,烟曲霉菌中唑类耐药的出现已成为一个主要问题,因为它们与治疗失败和死亡率增加有关.烟曲霉中唑类抗性的发展可通过获得性和内在机制发生。获得性抗性通常来自目标酶的突变，羊毛甾醇14-α-去甲基酶（Cyp51A），降低唑类抗真菌剂对酶的亲和力，使它们变得不那么有效，而固有抗性是指某些烟曲霉分离株由于固有的遗传特性而对唑类抗真菌剂的天然抗性。本综述旨在全面概述烟曲霉的唑类抗真菌药物耐药性，讨论了潜在的抗性机制，包括目标酶的改变，Cyp51A,以及外排泵参与药物外排。还探讨了唑类杀菌剂在环境中的使用以及抗性菌株的传播的影响。
