Mosquito-larvicidal Binary (BinA/B) proteins for mosquito control programs —advancements, challenges, and possibilities

The increasing global burden of mosquito-borne diseases require targeted, environmentally friendly, and sustainable approaches for effective vector control without endangering the non-target beneficial insect population. Biological interventions such as biopesticides, Wolbachia-mediated biological controls, or sterile insect techniques are used worldwide. Here we review Binary or BinAB toxin—the mosquito-larvicidal component of WHO-recognized Lysinibacillus sphaericus bacterium employed in mosquito control programs. Binary (BinAB) toxin is primarily responsible for the larvicidal effect of the bacterium. BinAB is a single-receptor-specific toxin and is effective against larvae of Culex and Anopheles, but not against Aedes aegypti. The receptor in Culex, the Cqm1 protein, has been extensively studied. It is a GPI-anchored amylomaltase and is located apically in the lipid rafts of the larval-midgut epithelium. The interaction of the toxin components with the receptor is crucial for the mosquito larvicidal activity of the BinAB toxin. Here we extend support for the pore formation model of BinAB toxin internalization and the role of toxin-glycan interactions in the endoplasmic reticulum in mediating larval death. BinAB is phylogenetically safe for humans, as Cqm1-like protein is not expected in the human proteome. This review aims to initiate targeted R&D efforts, such as applying fusion technologies (chimera of BinA, chemical modification of BinA), for efficient mosquito control interventions. In addition, the review also examines other areas such as bioremediation and cancer therapeutics, in which L. sphaericus is proving useful and showing potential for further development.