| Sumario: | Pesticide resistance represents a major challenge to global food production. The spread of resistance
alleles is the primary explanation for observations of reduced pesticide efficacy over time, but the
potential for gene-by-environment interactions (plasticity) to mediate susceptibility has largely
been overlooked. Here we show that nutrition is an environmental factor that affects susceptibility
to Bt toxins. Protein and carbohydrates are two key macronutrients for insect herbivores, and the
polyphagous pest Helicoverpa zea self-selects and performs best on diets that are protein-biased
relative to carbohydrates. Despite this, most Bt bioassays employ carbohydrate-biased rearing
diets. This study explored the effect of diet protein-carbohydrate content on H. zea susceptibility to
Cry1Ac, a common Bt endotoxin. We detected a 100-fold increase in LC50 for larvae on optimal versus
carbohydrate-biased diets, and significant diet-mediated variation in survival and performance when
challenged with Cry1Ac. Our results suggest that Bt resistance bioassays that use ecologically- and
physiologically-mismatched diets over-estimate susceptibility and under-estimate resistance.
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