From noxiustoxin to scorpine and possible transgenic mosquitoes resistant to malaria.

Scorpion venom contains different types of peptides toxic to a variety of organisms whose molecular targets have been described as mainly ion-channels of excitable cells where they cause impairment of function. Based on mouse, cricket, and crustacean bioassays, specific toxins for each group of animals have been found. Chromatographic techniques were used to isolate and chemically characterize these peptides. One of the best-studied peptides is noxiustoxin, a 39-amino acid residue-long peptide specific for K(+)-channels. Hadrurin is another scorpion venom peptide whose activity was shown to be bactericidal to a variety of species. Structural similarities of a newly discovered peptide (scorpine) with those of defensins and cecropins showed that scorpion venom contains peptides toxic to microorganisms and malaria parasites. Scorpine was shown to disrupt the sporogonic development of Plasmodium berghei. Using this system as a model for malaria, we introduced the gene of scorpine into a vector for generation of transgenic flies resistant to the infection by Plasmodium. The final aim of this work is to incorporate this gene under the promoter of proteolytic enzymes of digestive tract of mosquitoes for synthesis and liberation of toxic peptide(s) into stomach of freshly fed mosquitoes potentially carrying Plasmodium gametes. In this manner, a putative transgenic mosquito with these characteristics would secrete a toxic peptide with digestive enzymes into midgut, impairing proper development of Plasmodium, hence controlling malaria, one of the most important tropical diseases worldwide.