A chitin synthase mutation confers widespread resistance to buprofezin, a chitin synthesis inhibitor, in the brown planthopper, Nilaparvata lugens

Development of insecticide resistance in insect populations is a major challenge to sustainable agriculture and food security worldwide. Buprofezin, one of the commonly used chitin synthesis inhibitors, has severely declined its control efficacy against the brown planthopper (BPH, Nilaparvata lugens ), a devastating rice insect species. To date, however, mechanism of buprofezin resistance in target pests remains elusive. We conducted a long-term (25 years from 1996 to 2020) and large geographical scale (11 provinces and cities in China) resistance monitoring program for buprofezin in BPH, a notorious pest of rice crop in East and Southeast Asia. BPH rapidly developed resistance with > 1,000-fold resistance being detected in nearly all the field populations after 2015 . Using the bulk segregant mapping method, we uncovered a novel mutation (G932C) in chs1 gene encoding chitin synthase 1 from a near isogeneic buprofezin-resistant (> 10,000-fold) strain harboring recessive, monogenic resistance. Using CRISPR/Cas9-based genome-modified Drosophila melanogaster possessing the same mutation as a model, we found that the G932C mutation was not only responsible for buprofezin resistance but also conferred a cross-resistance to cyromazine, an insect molting disruptor, on which the mode of action is largely unknown. Taken together, our study for the first time revealed the molecular mechanism conferring buprofezin resistance in BPH and implicated that cyromazine also targets chitin biosynthesis to confer its toxicity.