Bacillus thuringiensis Crystal Toxin: Mechanisms of Resistance and Action

University Of California-San Diego, La Jolla CA

Investigators

Abstract

Crystal (Cry) proteins produced by the bacterium Bacillus thuringiensis (Bt) are the most important and widely used natural insecticides in the world today. These proteins are non-toxic to humans but very effective against insect pests that devastate crops and carry human diseases. As such, use of these protein toxins form a core element in the control of insect pests by: 1) organic farmers; 2) the World Health Organization in African mosquito/black fly abatement programs; and 3) transgenic cotton and corn plants that express them. The main scientific concern in the widespread use of these proteins is the development of resistance by the insects, which would render these crystal (Cry) protein toxins ineffective. To combat this threat, this project will study the mechanisms by which resistance to crystal proteins develop. Cry proteins that kill nematodes (roundworms) are similar to those that kill insects. Five genes have been identified that when mutated in the nematode C. elegans, render the nematode resistant to at least two Cry protein toxins. The normal function of these genes is to permit the Cry toxins to kill the roundworm. When any one of these is mutated, the Cry toxins cannot kill. This project will study the physical mechanisms in the roundworm by which mutation of these genes leads to resistance. Since at least one of these genes is found only in invertebrates and not in vertebrates, this project may also shed light on why nematodes and insects are normally killed by Cry toxins but vertebrates (including humans) are not. This project will also study a different group of genes call the "HYP" genes, so named because mutation of these genes lead to a HYPersensitive response. The function of these HYP genes is to normally provide some protection of the animal from Cry toxins so that when mutated, the animals succumb to the toxin more readily. An understanding of how the nematodes normally protect themselves from the toxic effects of Cry proteins may help us devise more effective ways to kill nematode and insect pests.