Department of Food, Environmental and Nutritional Science, University of Milan, via Celoria 2, 20900 Milano, Italy.
Department of Environmental Research and Innovation, Agro-Environmental Systems, Luxembourg Institute of Science and Technology, LIST, 5 Avenue des Hauts Fourneaux, L-4362 Esch-sur-Alzette, Luxembourg.
Pestic Biochem Physiol. 2020 Mar;164:209-220. doi: 10.1016/j.pestbp.2020.02.006. Epub 2020 Feb 4.
Demethylase inhibitors (DMIs) also referred to as azoles or triazoles are currently the main fungicides used for controlling Fusarium diseases and associated toxins in cereals. DMIs also represent an important class of fungicides used in the medical domain. The level of sensitivity of a set of F. graminearum strains (n = 23), collected over the period 1994-2010 in Luxembourg, Germany, Canada, USA, Italy and Belgium against three DMIs (cyproconazole, propiconazole, tebuconazole) used in agriculture and one DMI used in medicine (tioconazole) was assessed using a microplate test. Median molar EC values varied 113-fold among DMIs and on average 11-fold within DMIs with cyproconazole and tebuconazole being the least and the most effective ones, respectively. The EC values of the two DMIs registered for use against Fusarium species on cereals (propiconazole and tebuconazole) were significantly correlated (r = 0.597**), while no evidence for cross-resistance was obtained for other fungicide combinations. Haplotypes for CYP51A and CYP51C were defined based on snps determining amino acid variations in the two genes. EC values of strains with the CYP51A haplotype A0 and the CYP51C haplotype D1 varied greatly for the agricultural DMIs tebuconazole, propiconazole and cyproconazole, but not for the medical DMI tioconazole. None of the mutations and snps that were previously reported to be associated with resistance towards propiconazole was unambiguously related with resistance to tioconazole, because the mutations and snps were found in strains with low as well as with high EC values. Our results show that (1) DMI sensitivity of F. graminearum mycelium has been largely stable between 1994 and 2010, (2) effects of snps on sensitivity towards one DMI detected in one set of strains cannot be extrapolated to other DMIs and sets of strains and (3) F. graminearum strains responded differently to DMIs used in agriculture and to a representative of a medical DMI with no evidence for cross-resistance.
去甲基化酶抑制剂（DMIs）也称为唑类或三唑类，目前是用于控制谷物中镰刀菌病和相关毒素的主要杀菌剂。DMIs 也是医学领域中一类重要的杀菌剂。使用微量滴定板试验评估了 1994 年至 2010 年间在卢森堡、德国、加拿大、美国、意大利和比利时收集的一组 23 株禾谷镰刀菌（F. graminearum）菌株对农业中使用的三种 DMIs（环丙唑醇、丙环唑、戊唑醇）和一种医学上使用的 DMI（噻康唑）的敏感性。DMIs 之间的中值摩尔 EC 值差异为 113 倍，DMIs 内的 EC 值平均差异为 11 倍，其中环丙唑醇和戊唑醇的效果分别最小和最大。在谷物上针对镰刀菌属登记使用的两种 DMIs（丙环唑和戊唑醇）的 EC 值显著相关（r=0.597**），而对于其他杀菌剂组合则没有获得交叉抗性的证据。基于确定两个基因中氨基酸变化的 SNP 定义了 CYP51A 和 CYP51C 的单倍型。对于农业 DMIs 戊唑醇、丙环唑和环丙唑醇，具有 CYP51A 单倍型 A0 和 CYP51C 单倍型 D1 的菌株的 EC 值差异很大，但对于医学 DMI 噻康唑则没有。先前报道与丙环唑抗性相关的突变和 SNP 与对噻康唑的抗性没有明确关系，因为在 EC 值低和高的菌株中都发现了这些突变和 SNP。我们的研究结果表明：（1）1994 年至 2010 年间，禾谷镰刀菌菌丝体对 DMI 的敏感性基本保持稳定；（2）在一组菌株中检测到的对一种 DMI 的 SNP 对其他 DMIs 和菌株集的敏感性的影响不能外推；（3）禾谷镰刀菌菌株对农业中使用的 DMIs 和医学 DMI 的代表性药物的反应不同，没有交叉抗性的证据。
