Pyflubumide is a novel selective carboxanilide acaricide that inhibits mitochondrial complex II of spider mite species such as Tetranychus urticae. We explored the baseline toxicity and potential cross-resistance risk of pyflubumide in a reference panel of T. urticae strains resistant to various acaricides with different modes of action. A cyenopyrafen-resistant strain (JPR) was identified as the only strain with low-to-moderate level of cross-resistance to pyflubumide (LC₅₀ = 49.07 mg/L). In a resistance risk assessment approach, JPR was subsequently selected which led to two highly resistant strains JPR-R1 (RR = 466.7) and JPR-R2 (RR = 614.8). Interestingly, compared to adult females, resistance was much less pronounced in adult males and eggs of the two JPR-R strains. In order to elucidate resistance mechanisms, we first sequenced the complex II subunits in susceptible and resistant strains, but target-site insensitivity could not be detected. In contrast, synergism/antagonism experiments strongly suggested that cytochrome P450 monooxygenases are involved in pyflubumide resistance. We therefore conducted genome-wide gene expression experiments to investigate constitutive and induced expression patterns and documented the overexpression of five cytochrome P450 and four carboxyl/choline esterase genes in the JPR-R strains after pyflubumide exposure. Together, we provide a first resistance risk assessment of a novel complex II inhibitor and provide first evidence for metabolic resistance mediated by cytochrome P450s in T. urticae.

中文翻译：

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新型复合物II抑制剂吡氟溴醚对多食性害虫Tetranychus urticae的抗药性风险评估

吡氟脲是一种新型的选择性羧胺杀螨剂，可以抑制红蜘蛛（Tetranychus urticae）等蜘蛛螨的线粒体复合物II 。我们探讨了基线毒性和pyflubumide的潜在交叉耐药性的风险中的基准面板T.螨菌株与不同作用模式的不同杀螨剂抗药性。赛诺吡芬抗性菌株（JPR）被确定为唯一对吡氟溴胺具有低至中等交叉抗性水平的菌株（LC ₅₀ = 49.07 mg / L）。在抗药性风险评估方法中，随后选择了JPR，这导致了两个高抗药性菌株JPR-R1（RR = 466.7）和JPR-R2（RR = 614.8）。有趣的是，与成年雌性相比，两种JPR-R菌株的成年雄性和卵中的抗药性不明显。为了阐明抗药性机制，我们首先对易感和抗药性菌株中的复杂II亚基进行了测序，但是无法检测到靶位不敏感。相反，协同/拮抗实验强烈提示细胞色素P450单加氧酶与pyflubumide耐药有关。因此，我们进行了全基因组基因表达实验，以研究组成型和诱导型表达模式，并记录了氟吡溴铵暴露后JPR-R菌株中五个细胞色素P450和四个羧基/胆碱酯酶基因的过表达。我们在一起提供了一种新型复合物II抑制剂的首次耐药风险评估，并为由细胞色素P450介导的代谢耐药提供了初步证据。T.螨。