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Pest Manag Sci. 2017 Oct;73(10):1987-1993. doi: 10.1002/ps.4607. Epub 2017 Jul 24.
Azole resistance in human fungal pathogens has increased over the past twenty years, especially in immunocompromised patients. Similarities between medical and agricultural azoles, and extensive azole (14α-demethylase inhibitor, DMI) use in crop protection, prompted speculation that resistance in patients with aspergillosis originated in the environment. Aspergillus species, and especially Aspergillus fumigatus, are the largest cause of patient deaths from fungi. Azole levels in soils following crop spraying, and differences in sensitivity between medical and agricultural azoles (DMIs), indicate weaker selection in cropping systems than in patients receiving azole therapy. Most fungi have just one CYP51 paralogue (isozyme CYP51B), but in Aspergillus sp. mutations conferring azole resistance are largely confined to a second paralogue, CYP51A. Binding within the active centre is similar for medical and agricultural azoles but differences elsewhere between the two paralogues may ensure selection depends on the DMI used on crops. Two imidazoles, imazalil and prochloraz, have been widely used since the early 1970s, yet unlike triazoles they have not been linked to resistance in patients. Evidence that DMIs are the origin, or increase the frequency, of azole resistance in human fungal pathogens is lacking. Limiting DMI use would have serious impacts on disease control in many crops, and remove key tools in anti-resistance strategies. © 2017 Society of Chemical Industry.
唑类抗药性在过去二十年中不断增加，尤其是在免疫功能低下的患者中。医学和农业用唑类药物之间存在相似性，以及在作物保护中广泛使用唑类（14α-去甲基酶抑制剂，DMI），这促使人们猜测曲霉病患者的耐药性源于环境。曲霉菌属，尤其是烟曲霉，是导致真菌感染患者死亡的主要原因。作物喷洒后的土壤中唑类药物的含量，以及医学和农业唑类药物（DMIs）之间的敏感性差异，表明在作物种植系统中的选择压力比接受唑类药物治疗的患者要小。大多数真菌只有一个 CYP51 同源物（同工酶 CYP51B），但在 Aspergillus sp. 中，赋予唑类耐药性的突变主要局限于第二个同源物 CYP51A。医学和农业唑类药物在活性中心的结合相似，但两个同源物之间的其他差异可能确保选择取决于在作物上使用的 DMI。两种咪唑类杀菌剂，咪鲜胺和丙环唑，自 20 世纪 70 年代初以来就被广泛使用，但与三唑类药物不同，它们与患者的耐药性无关。缺乏证据表明 DMIs 是人类真菌病原体唑类耐药性的起源或增加频率。限制 DMI 的使用将对许多作物的疾病控制产生严重影响，并消除抗耐药性策略中的关键工具。© 2017 英国化学学会。
