One of the agents most used in the microbial control of pests is the bacterium Bacillus thuringiensis (Bt). During sporulation, this bacterium synthesises especial proteins that aggregate to form a parasporal crystal which can reach, in some strains, the same size as the spore. When insects ingest the sporulated bacterium, in addition to the spore they also ingest the crystal. This is dissolved in the intestine where it releases its protein components (protoxins) which, normally, have to be activated by intestine proteases to their toxic final form. The toxin then binds to receptors in the epithelial membrane of the intestine forming pores in the cells which eventually kill the insect. This poisoning facilitates germination of the spore and invasion of its host. Other insecticidal proteins produced by Bt during the vegetative phase of growth (the Vip proteins) also follow similar steps in their mode of action, though they target different membrane receptors.

Some advantages of using these pathogens in the fight against insects are, on the one hand, their specificity, since one can target the pest insect without affecting the beneficial insect populations and, on the other hand, they are totally innocuous to organisms other than insects, including humans. These characteristics make the insecticides based on Bt a resource very appreciated from the standpoint of the organic farming. As a matter of fact, they are of the very few insecticides allowed in this type of agriculture. Another advantage which Bt has is that, because the toxin is a protein, genes can be isolated in the laboratory and transferred to other organisms. In fact, the reason why this bacterium is so popular is because of its use in genetic engineering. Genes from Bt have been transferred to plant genomes and when these plants express the insecticidal proteins become resistant to the insects that normally feed on them. Since 1996, many crops of commercial interest have been transformed to become resistant to their main pests, the so called Bt-crops, which nowadays are extensively planted world-wide.

The search for new Bt genes that codify for new insecticidal proteins will allow to broaden the spectrum of action of Bt-based insecticides. This is of great interest not just to fight pests that are not controlled at present by this type of insecticides, but to obtain toxins that will maintain their effectiveness to control insect populations when these start to develop resistance to toxins currently in use from this bacterium.

The problem of insect resistance is a very important one as it can render an insecticide obsolete in a few years. This problem does not only affect chemical insecticides, but it also affects microbial insecticides. The understanding of the mechanisms by which Bt toxins work, and by which an insect can become resistant to them, can help to design strategies to prevent resistance from appearing. The results of this type of research are very useful to design strategies for the utilisation of Bt-based insecticides to minimise the possibility of resistance appearing and, in this way, to ensure that this insecticide, which has such useful characteristics, continues to be in use. But this understanding is especially relevant in the context of the design of insect resistant transgenic crops, since the correct selection of genes (which codify Bt toxins) to be introduced in a plant will depend on their mode of action. A plant expressing two toxins that use the same target site for their action will provoke the appearance of resistance in the pest insects much faster than one expressing two toxins that use different target sites.

Our general objective is to study the potential of insects to develop resistance to toxins from Bt and the genetic and biochemical basis of this resistance. This is a basic line of research, though with an applied projection, in which we work since the end of 1989.

Funding for this research has been obtained from public sources such as the European Union, the NATO, the Bill and Melinda Gates Foundation, the Spanish Ministry of Science and Education (through its different names along the years), and the Generalitat Valenciana (the Autonomic Government), as well as from private companies, such as Bayer CropScience and Dow Agrosciences.