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解偶联剂 SYP-14288 通过细胞色素 P450 单加氧酶和 P-糖蛋白的过度表达诱导辣椒疫霉菌的多药耐药性。

Uncoupler SYP-14288 inducing multidrug resistance of Phytophthora capsici through overexpression of cytochrome P450 monooxygenases and P-glycoprotein.

机构信息

College of Plant Protection, Northwest A&F University, 3 Taicheng Road, Yangling, 712100, China.

College of Plant Protection, China Agricultural University, 2 Yuanmingyuanxi Road, Beijing, 100193, China.

出版信息

Pest Manag Sci. 2022 Jun;78(6):2240-2249. doi: 10.1002/ps.6845. Epub 2022 Mar 14.

DOI:10.1002/ps.6845
PMID:35191608
Abstract

BACKGROUND

Fungicide resistance has become a serious problem for different mode of action groups except for uncouplers, which makes their resistance mechanism a hot topic, which until now, has not been well clarified. SYP-14288, a newly developed diarylamine fungicide modeled on fluazinam, has shown good toxicity to both oomycete and fungus by the action of uncoupling. In this research, the resistance of Phytophthora capsici to SYP-14288 was studied to clarify the resistance mechanism of uncouplers.

RESULTS

The toxicity tests of resistant strains against SYP-14288 showed multidrug resistance. The high-performance liquid chromatography (HPLC) results showed that resistant strains could efflux the fungicide, and this ability could be inhibited by the efflux pump inhibitor amitriptyline. The target protein of amitriptyline is P-glycoprotein (P-gp), which was overexpressed in resistant strains. Three products of nitrate reduction of SYP-14288 were detected and determined by HPLC-Q-TOF. Eight cytochrome P450 monooxygenase (P450) proteins were differentially involved in the reduction reaction.

CONCLUSION

Both fungicide efflux and detoxification metabolism were involved in the resistance mechanisms of P. capsici to SYP-14288. © 2022 Society of Chemical Industry.

摘要

背景

除解偶联剂外,不同作用模式类别的杀真菌剂的抗药性已成为一个严重的问题,这使得它们的抗药性机制成为一个热门话题,但至今尚未得到很好的阐明。SYP-14288 是一种新型的二苯胺类杀真菌剂,其结构模拟氟唑菌酰胺,通过解偶联作用对卵菌和真菌均显示出良好的毒性。本研究对辣椒疫霉菌对 SYP-14288 的抗药性进行了研究,以阐明解偶联剂的抗药性机制。

结果

抗性菌株对 SYP-14288 的毒性测试显示出多药耐药性。高效液相色谱(HPLC)结果表明,抗性菌株可以外排杀真菌剂,而这种能力可以被外排泵抑制剂阿米替林抑制。阿米替林的靶蛋白是 P 糖蛋白(P-gp),它在抗性菌株中过表达。通过 HPLC-Q-TOF 检测和确定,检测到 SYP-14288 的硝酸盐还原的三种产物。有 8 种细胞色素 P450 单加氧酶(P450)蛋白参与还原反应。

结论

辣椒疫霉菌对 SYP-14288 的抗药性机制涉及到杀菌剂外排和解毒代谢。 © 2022 化学工业协会。

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