Electrical hypothesis of toxicity of the Cry toxins for mosquito larvae.
Many electrical properties of insect larval guts have been studied, but their importance for toxicity of the Cry-type toxins has never been reported in the literature. In the present work, we observed potential-dependent permeabilization of plasma membrane by several polycationic peptides derived from the Cry11Bb protoxin. The peptide BTM-P1d, all D-type amino acid analogue of the earlier reported peptide BTM-P1, demonstrated high membrane-permeabilizing activity in experiments with isolated rat liver mitochondria, RBC (red blood cells) and mitochondria in homogenates of Aedes aegypti larval guts. Two larger peptides, BTM-P2 and BTM-P3, as well as the Cry11Bb protoxin treated with the protease extract of mosquito larval guts showed similar effects. Only protease-resistant BTM-P1d, in comparison with other peptides, displayed A. aegypti larval toxicity. Taking into account the potential-dependent mechanism of membrane permeabilization by studied fragments of the Cry11Bb protoxin and the literature data related to the distribution of membrane and transepithelial potentials in the A. aegypti larval midgut, we suggest an electrical hypothesis of toxicity of the Cry toxins for mosquito larvae. According to this hypothesis, the electrical field distribution is one of the factors determining the midgut region most susceptible for insertion of activated toxins into the plasma membrane to form pores. In addition, potential-dependent penetration of short active toxin fragments into the epithelial cells could induce permeabilization of mitochondria and subsequent apoptosis or necrosis.
Escuela de Física Universidad Nacional de Colombia, sede Medellín, Calle 59-A, No. 63-20, Medellín, Colombia. vvasilie@unal.edu.co
Victor V
VV
Lemeshko
Sergio
S
Orduz
D000330:Aedes / Q000187:drug effects*; D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology; D017209:Apoptosis; D001426:Bacterial Proteins / Q000737:chemistry / Q000494:pharmacology*; D001427:Bacterial Toxins / Q000737:chemistry / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects; D002463:Cell Membrane Permeability; D045304:Cytochromes c / Q000737:chemistry; D004563:Electrochemistry / Q000379:methods; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism; D004912:Erythrocytes / Q000187:drug effects; D006868:Hydrolysis; D007306:Insecticides / Q000494:pharmacology; D007814:Larva / Q000187:drug effects; D008099:Liver / Q000187:drug effects*; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D008969:Molecular Sequence Data; D009249:NADP / Q000737:chemistry; D010084:Oxidation-Reduction; D010572:Pest Control, Biological / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility
D023181:Antimicrobial Cationic Peptides; C501422:BTM-P1 peptide; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C115468:CRY11BB protein, Bacillus thuringiensis; D007306:Insecticides; D009249:NADP; D045304:Cytochromes c