This review examines Bacillus thuringiensis subsp. israelensis (Bti) as both a highly selective microbial larvicide and a biological platform for protein storage and delivery, enabled by the structural features of its prokaryotic insect larvicidal organelle (PILO). Bti remains the most widely deployed biological agent for mosquito control. Decades of operational use demonstrate substantial public health benefits and only limited, manageable ecological tradeoffs within integrated vector management programs (IVMP). Its narrow host range underlies an excellent safety record for humans and other vertebrates. Moreover, laboratory and field studies consistently show that collateral effects are minimal, context dependent, reversible, and largely restricted to closely related non-target aquatic dipterans. These attributes have established Bti as a cornerstone of environmentally sustainable IVMP worldwide. Here, we synthesize current knowledge on Bti biology, ecological selectivity, field performance, and the resistance-management properties embedded in the molecular architecture of the PILO. Finally, we assess emerging opportunities and technical constraints in repurposing the PILO as an in vivo microbial factory for packaging heterologous proteins with potential pharmaceutical and industrial applications.

Bacillus thuringiensis subsp. israelensis (Bti) is the most widely used biological larvicide for mosquito control worldwide and a cornerstone of environmentally sustainable vector-management programs. Its long-term global deployment reflects a well-characterized balance between public-health benefit and manageable ecological tradeoffs within integrated vector management (IVM) frameworks. Bti combines high larvicidal efficacy, operational simplicity, and strong target specificity, resulting in an exceptional safety profile for humans and vertebrate wildlife. Decades of laboratory and field studies demonstrate that Bti is biologically selective rather than ecologically inert, with reproducible yet context-dependent effects confined to closely related non-target aquatic dipterans. This review links the molecular and toxicological foundations of Bti to its operational performance, ecological selectivity, resistance-mitigating properties, and sustained utility in mosquito-control programs. Beyond its established larvicidal function, Bti’s prokaryotic insect larvicidal organelle (PILO) represents an underexplored platform for heterologous intracellular protein assembly. Its dense packing, structural stability, and resistance to environmental and biochemical stress indicate an evolutionary specialization for high-capacity protein storage during sporulation. These properties support noncanonical applications in biomolecule storage and stabilization and motivate cautious exploration of environmentally responsive protein release strategies. Although significant mechanistic and translational challenges remain, particularly with respect to cargo trafficking, modularity, and purification, the architectural principles that have enabled effective mosquito control provide a strong foundation for extending PILO-based platforms beyond larvicidal applications.