Bacillus thuringiensis Cry and Cyt Toxins: Mechanisms of Action, Resistance Management and Impact on Host Immune Responses

Bacillus thuringiensis (Bt) is a pioneering biopesticide known for its potent insecticidal proteins, particularly Cry and Cyt toxins which have transformed agricultural pest management worldwide. As a naturally occurring bacterium, Bt is favored for its environmentally friendly profile and high specificity toward target insect pests, significantly reducing reliance on synthetic chemical pesticides. This review focused on the mechanisms of action of Bt toxins, their specificity and the implications for pest management strategies. Cry toxins are produced as inactive protoxins that undergo proteolytic activation in the alkaline environment of the insect midgut. This activation triggers a conformational change, enabling the protoxins to bind to specific receptors on midgut epithelial cells such as cadherins, aminopeptidases and alkaline phosphatases. These binding initiates biological events that lead to pore formation, cell lysis and ultimately, insect mortality. The specificity of Cry toxins largely depends on their interactions with these receptors, which vary among different insect species. In contrast, Cyt toxins employ a different mechanism by directly interacting with lipid bilayers to form pores, allowing them to target a broader spectrum of insect pests, including those resistant to Cry toxins. Recent research has shed light on the structural details of toxin-receptor interactions and pore formation mechanisms, facilitating the development of novel Bt toxins with enhanced efficacy and broader activity spectra. Insights from genomic studies on resistance mechanisms have revealed critical information about receptor gene mutations and midgut protease activity alterations, essential for developing targeted solutions against resistance. The environmental and non-target effects of Bt toxins are also crucial considerations. Current research indicates that Bt toxins generally have minimal adverse impacts on beneficial insects, soil microbiota and aquatic ecosystems, underscoring their ecological safety profile.