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The soil bacterium Bacillus thuringiensis (Bt) is the most successfully used biopesticide in agriculture, and its insecticidal protein genes are the primary transgenes used for insect control in transgenic crops. However, evolution of insect resistance to Bt toxins threatens the long-term future of Bt applications. To date, cases of resistance to Bt toxins have been reported in agricultural situations in six insect species, but the molecular basis for these cases of resistance remains unclear. Here we report that the resistance to the Bt toxin Cry1Ac in the cabbage looper, Trichoplusia ni, evolved in greenhouses, is associated with differential alteration of two midgut aminopeptidases N, APN1 and APN6, conferred by a trans-regulatory mechanism. Biochemical, proteomic, and molecular analyses showed that in the Cry1Ac-resistant T. ni, APN1 was significantly down-regulated, whereas APN6 was significantly up-regulated. The Cry1Ac resistance was correlated with down-regulation of APN1 but not with the up-regulation of APN6. The concurrent up-regulation of APN6 and down-regulation of APN1 might play a role in compensating for the loss of APN1 to minimize the fitness costs of the resistance. Along with identifying reduced expression of APN1 as the molecular basis of Bt resistance selected in an agricultural setting, our findings demonstrate the importance of APN1 to the mode of action of Bt toxin Cry1Ac.

Differential alteration of two aminopeptidases N associated with resistance to Bacillus thuringiensis toxin Cry1Ac in cabbage looper