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Paracoccus marginatus papaya mealybugs cause considerable threats and challenges to cassava production and processing. The deployment of resistant cultivars offers effective, economical and eco-friendly management strategies for pest management. We measured P. marginatus mortality, development and reproduction to evaluate the resistance of fifteen cassava cultivars and conducted physiological and biochemical analyses when P. marginatus was fed on two resistant cultivars (Myanmar and C1115) and three susceptible cultivars (BRA900, Bread, SC205). Significantly lower digestive (amylase, sucrase, lipase), detoxification (glutathione-S-transferase and carboxylesterase) and antioxidant activity, including superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and polyphenol oxidase (PPO), enzyme activities were observed in P. marginatus feeding on resistant cultivars compared to susceptible cultivars. For resistant cultivars, a significant reduction was found in nutritional components containing free amino acids, nitrogen, soluble sugars and the secondary metabolite malondialdehyde. Additionally, significantly higher enzymatic activity (SOD, CAT, POD and PPO) levels and secondary metabolite quantities (total phenol and tannins) were found in resistant cultivars induced by P. marginatus compared with susceptible ones. Additionally, RT-qPCR tests showed that the transcripts of ten genes involved in nutrition, secondary metabolites and antioxidant activities were consistent with physiology changes. Thus, the resistant cultivars suffered lower P. marginatus damage by elevating secondary metabolite contents and antioxidant activities, reducing plant nutrition levels and decreasing insect enzymatic activities. This study will be beneficial in developing indices for standard regulation to evaluate P. marginatus-resistant cassavas and effectively manage this pest. [ABSTRACT FROM AUTHOR]