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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
Published on: October 25, 2013
Both target-site and non-target-site resistance mechanisms confer mesosulfuron-methyl resistance in Silene conoidea L
Xinhui Xue1, Hailan Cui2, Shen'ao Hu1
1State Key Laboratory for Biology of Plant Diseases and Insect Pests, Institute of Plant Protection, Chinese Academy of Agricultural Sciences, Beijing 100193, China; College of Plant Protection, Northeast Agricultural University, Harbin 150030, China.
Abstract:
Silene conoidea L., a common weed in wheat fields, is mainly controlled by acetolactate synthase (ALS)-inhibiting herbicides such as mesosulfuron-methyl. In this study, we investigated a mesosulfuron-methyl resistant population to elucidate the resistance mechanisms. The resistant (R) population displayed a high level of resistance to mesosulfuron-methyl, with the resistance index (RI) of 18.87. It also exhibited cross-resistance to halosulfuron-methyl, florasulam, flumetsulam, and flucarbazone‑sodium. In vitro ALS enzyme activity in the R population was 22.85-fold higher than in the susceptible (S) population. A W574L mutation (leucine replaced tryptophan) was identified in the ALS gene of the R population. Through molecular docking, this substitution of amino acid weakened the π-π stacking interaction between mesosulfuron-methyl molecule and the non-mutated ALS enzyme. The R population also showed significantly higher ALS expression than the S population, while the ALS gene copy number did not differ between the two populations. Pretreatment with malathion (cytochrome P450 inhibitor) and NBD-Cl (glutathione S-transferases inhibitor) reduced mesosulfuron-methyl resistance by 43.92 % and 29.20 %, respectively. Indicating that CYP450s and GSTs are involved in resistance. Transcriptome and qPCR analyses identified significant upregulation of three ABC transporter genes, three CYP450 genes, and one GST gene in the R population. Meanwhile, KEGG pathway analysis indicated that the photosynthetic pathways were significantly affected after mesosulfuron-methyl treatment. This is the first report of mesosulfuron-methyl resistance in S. conoidea, involves both target site resistance and non-target site resistance mechanisms.
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