As an alternative to synthetic chemical pesticides, insecticidal Cry proteins from the bacterium Bacillus thuringiensis (Bt) provide a safer and more environmentally friendly approach to controlling insect pests. After ingestion, the Cry delta-endotoxin proteins bind to and destroy insect midgut cells. These proteins are preferred over chemical insecticides because they show more host specificity and degrade more rapidly in the environment. Insecticides derived from a number of subspecies of Bt are available commercially to control caterpillars, potato beetle, mosquitoes and blackflies. In addition, transgenic insect resistant cotton, potatoes, corn, and tomatoes that express Cry genes have passed U.S. regulatory review and are now being grown commercially.

One of the concerns with any insecticide, whether it be biological, naturally- occurring, or synthetic, is the evolution of an insect population resistant to the active ingredient. So long as it does not lead to cross-resistance to related compounds, development of resistance to a specific pesticide is a manageable problem. A rotation strategy using different insecticides can effectively minimize the probability of developing insects resistant to any one compound.

Enthusiasm for Bt as a biological pest control agent has been tempered, however, by the appearance of Bt-resistant insects in field populations of diamondback moth, some of which show cross-resistance to a number of different Cry proteins. This observation means that a simple rotation of Cry proteins would not be an effective resistance management strategy.

A potential method to overcome the development of insects resistant to Bt Cry proteins has arisen from studies with the Bt subspecies israelensis, which has been effectively used to control larvae of mosquitoes and blackflies. No confirmed resistance to Bt israelensis in field populations of mosquitoes has been reported, possibly because its insecticidal activity differs from other Bt subspecies. In addition to the Cry proteins, Bt israelensis produces a unique cytotoxic protein called CytA, which has a different cellular target than the Cry proteins.

The unique mode of action of CytA and its ability to act synergistically with Cry proteins may account for the inability of mosquitoes to develop resistance to Bt israelensis. Researchers at the University of California, Riverside have reported that high (100- to 1,000-fold) levels of resistance to Cry proteins in mosquito larvae can be suppressed or markedly reduced by combining Cry proteins with sublethal levels of CytA.

Because CytA is known to be active against only a limited group of flies, primarily larvae of mosquitoes and blackflies, the widespread application of this strategy for overcoming Bt resistance in agriculturally important pests may be limited. However, it has been recently found that CytA is also active against the cottonwood leaf beetle. This raises the hope that the CytA/Cry model will lead to development of a second generation of biological insecticides that can overcome the development of Bt resistance in other insects.

Reference
Wirth, M.C., Georghiou, G.P., and Federici, B.A. 1997. CytA enables CryIV endotoxins of Bacillus thuringiensis to overcome high levels of CryIV resistance in the mosquito Culex quinquefasciatus. Proc. Natl. Acad. Sci. USA 94:10536- 10540.