The ability to transmit viruses, bacteria and parasites responsible for such
diseases as malaria, dengue fever and chikungunya make mosquitoes one of the most harmful organisms to human health. To reduce mosquito populations, most countries use chemical insecticides that not only generate resistance but are also toxic to many cold-blooded animals such as bees, crustaceans and fish. So, how can mosquito populations be reduced without impacting the environment or inducing resistance?
This is where Bacillus thuringiensis (often abbreviated to Bt), a species of bacteria used for its insecticidal properties, comes into play. Bt can also refer generically to pesticide molecules known as thuringiensins, which are the toxins produced by this bacterium. Bacillus thuringiensis israelensis (Bti) produces four toxins in the form of nanocrystals that specifically target mosquito larvae. After the ingestion of these crystals by mosquito larvae, they dissolve in the intestine and oligomerize in the membranes of intestinal cells thanks to the action of enzymes (digestive protoxins). Consequently, the larva’s intestine is perforated, resulting in its death.
Leading a consortium of 11 laboratories, researchers from the Irig have focused on Cyt1Aa, one of these four toxins. Cyt1Aa is a specific toxin that is capable of interacting directly with the membranes of mosquito intestinal cells, and for which no resistance has been observed to date in Bti-treated areas. Combining several approaches in structural biology, molecular biology, biochemistry, biophysics and toxicology, the researchers have elucidated the activation cascade of Cyt1Aa, all the way from its crystallization within the bacterium to its toxic activity in the insect.
By providing a detailed understanding of the crystallization mechanisms of Cyt1Aa and its role in the digestive tract of mosquitoes, this work paves the way for a rational adaptation of the properties of this natural toxin. This includes perspectives for extending its spectrum of action, increasing its toxicity and reducing production costs, thereby enabling the wide use of this mosquito repellent without danger to the environment.
Interdisciplinary Research Institute of Grenoble (IRIG - CEA/CNRS/Université Grenoble Alpes), France
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Lawrence Berkeley National Laboratory, US
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SLAC National Accelerator Laboratory, US
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European Synchrotron Radiation Facility, France
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University of California, US
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Jacobs University, Bremen, Germany
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Institut Laue-Langevin, France
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