Cai Meng, Zhang Can, Wang Weizhen, Peng Qin, Song Xi, Tyler Brett M, Liu Xili
College of Plant Protection China Agricultural University Beijing China.
College of Chemistry Key Laboratory of Pesticide & Chemical Biology of Ministry of Education Central China Normal University Wuhan China.
Evol Appl. 2020 Dec 31;14(4):996-1008. doi: 10.1111/eva.13176. eCollection 2021 Apr.
Flumorph is a carboxylic acid amide (CAA) fungicide with high activity against oomycetes. However, evolution to CAAs from low resistance to high resistance has never been reported. This study investigated the basis of resistance evolution of flumorph in . Total of 120 isolates were collected and their sensitivity to flumorph was evaluated. Although no spontaneous resistance was found among the field isolates, adaptation on flumorph-amended media resulted in the selection of five stable mutant types exhibiting varying degrees of resistance to CAAs. Type I, which exhibited the lowest resistance level, was obtained when the wild-type isolate was exposed to a low concentration of flumorph, but no resistant mutants were obtained by direct exposure to higher concentrations. However, the more resistant types (Type II, III, IV and V) were obtained when Type I were exposed to higher concentrations of flumorph. Similar results were obtained when the entire screening process was repeated, which implied that evolution of resistance to flumorph in could be a two-step process, where high resistance phenotypes could develop gradually from low resistance ones. Further investigation into molecular mechanism strongly confirmed that evolution of isolates highly resistant to flumorph occurs in a stepwise process with Type I as intermediary, through accumulation of mutations in their target protein of CAAs (CesA3). Together, our findings indicate that application of low rates of flumorph in field could result in selection of low resistance Type I isolates, but that raising dosage to maintain comparable levels of control could elicit rapid evolution of more resistant Type II, III, IV and V isolates with stepwise accumulation of mutations in CesA3, which would render flumorph ineffective as a control method. Precautionary resistance management strategy should be implemented. The phenomenon described in the study could have broader biological significance.
氟吗啉是一种对卵菌具有高活性的羧酸酰胺（CAA）类杀菌剂。然而，从低抗性到高抗性向CAA类杀菌剂的抗性进化从未有过报道。本研究调查了[具体对象未提及]中氟吗啉抗性进化的基础。总共收集了120个分离株，并评估了它们对氟吗啉的敏感性。虽然在田间分离株中未发现自发抗性，但在含氟吗啉的培养基上适应培养后，筛选出了5种对CAA类杀菌剂表现出不同程度抗性的稳定突变类型。I型表现出最低的抗性水平，是野生型分离株暴露于低浓度氟吗啉时获得的，但直接暴露于较高浓度时未获得抗性突变体。然而，当I型暴露于更高浓度的氟吗啉时，获得了抗性更强的类型（II型、III型、IV型和V型）。重复整个筛选过程时也得到了类似结果，这表明[具体对象未提及]中对氟吗啉的抗性进化可能是一个两步过程，高抗性表型可从低抗性表型逐渐发展而来。对分子机制的进一步研究有力地证实，对氟吗啉高度抗性的分离株的进化是一个逐步过程，以I型为中间阶段，通过其CAA类杀菌剂的靶蛋白（CesA3）中的突变积累实现。总之，我们的研究结果表明，在田间低剂量使用氟吗啉可能导致低抗性I型分离株的选择，但提高剂量以维持相当的防治水平可能会引发抗性更强的II型、III型、IV型和V型分离株的快速进化，CesA3中突变逐步积累，这将使氟吗啉作为一种防治方法失效。应实施预防性抗性管理策略。该研究中描述的现象可能具有更广泛的生物学意义。
