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 EC50 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 EC50 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. EC50 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 EC50 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.

中文翻译：

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寻找禾谷镰刀菌田间菌株对四种去甲基酶抑制剂敏感性差异的分子决定因素

脱甲基酶抑制剂 (DMIs) 也称为唑类或三唑类，是目前用于控制谷物中镰刀菌病和相关毒素的主要杀菌剂。DMI 也代表了一类重要的用于医疗领域的杀菌剂。1994-2010 年在卢森堡、德国、加拿大、美国、意大利和比利时收集的一组禾谷镰刀菌菌株（n = 23）对农业中使用的三种 DMI（环丙康唑、丙环唑、戊唑醇）的敏感性水平使用微孔板测试评估了一种用于医学的 DMI（噻康唑）。中位摩尔 EC50 值在 DMI 之间变化 113 倍，在 DMI 内平均变化 11 倍，其中环丙康唑和戊唑醇分别是最不有效和最有效的。注册用于对抗谷物上镰刀菌属物种的两种 DMI（丙环唑和戊唑醇）的 EC50 值显着相关（r = 0.597**），而没有获得其他杀菌剂组合的交叉抗性证据。CYP51A 和 CYP51C 的单倍型是基于确定两个基因中氨基酸变异的 snps 来定义的。CYP51A 单倍型 A0 和 CYP51C 单倍型 D1 菌株的 EC50 值对于农用 DMI 戊唑醇、丙环唑和环丙康唑差异很大，但对于医用 DMI 噻康唑则没有差异。先前报道的与丙环唑耐药性相关的突变和 snps 都与噻康唑耐药性无关，因为在 EC50 值低和高的菌株中都发现了突变和 snps。