B acillus thuringiensis insecticidal three‐domain C ry toxins: mode of action, insect resistance and consequences for crop protection

B acillus thuringiensis bacteria are insect pathogens that produce different C ry and C yt toxins to kill their hosts. Here we review the group of three‐domain C ry (3d‐ C ry) toxins. Expression of these 3d‐ C ry toxins in transgenic crops has contributed to efficient control of insect pests and a reduction in the use of chemical insecticides. The mode of action of 3d‐ C ry toxins involves sequential interactions with several insect midgut proteins that facilitate the formation of an oligomeric structure and induce its insertion into the membrane, forming a pore that kills midgut cells. We review recent progress in our understanding of the mechanism of action of these C ry toxins and focus our attention on the different mechanisms of resistance that insects have evolved to counter their action, such as mutations in cadherin, APN and ABC transporter genes. Activity of C ry1 AM od toxins, which are able to form toxin oligomers in the absence of receptors, against different resistant populations, including those affected in the ABC transporter and the role of dominant negative mutants as antitoxins, supports the hypothesis that toxin oligomerization is a limiting step in the C ry insecticidal activity. Knowledge of the action of 3d‐ C ry toxin and the resistance mechanisms to these toxins will set the basis for a rational design of novel toxins to overcome insect resistance, extending the useful lifespan of C ry toxins in insect control programs.