Journal of Clinical Toxicology
Open Access

The Potency of Bacillus thuringiensis Cry and Cyt Toxins and their Host Action

Jonathan Adam^{* *}Correspondence: Jonathan Adam, Department of Biomedicine, Swammerdam Institute of Life Sciences, University of Amsterdam, Amsterdam, The Netherlands, Email:

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Description

Bacillus thuringiensis is a gram-positive, rod-shaped soil bacterium that has been detached from a wide range of ecosystems, such as soil, water, dead insects, dust from silos, and leaves from deciduous trees, diverse conifers, and insectivorous mammals. It is best known for its ability to produce crystalline components (Cry toxins) during sporulation, which contain insecticidal proteins called endotoxin. Bt crystalline inclusions have been shown to be toxic to a wide range of insect pests, including Lepidoptera, Coleoptera, and Diptera, as well as Hemipterans, as well as other biological activities like molluscicidal, nematicide (human and animal parasites, and free living; Rhabditida), acaricide, and even human cancer cells.

Humans metabolize Cry toxins just like any other protein found in foods including meat, beans, leafy greens, and tofu, according to studies. Cry toxins come in a variety of forms, each with various degrees of insect specificity (primarily moths and butterflies, beetles, and flies). To treat multiple pests at once, Cry poisons can be blended and matched. These proteins toxicity is very selective to insect larvae, causing death in a variety of insect species but not in humans or other animals. By entering into the target membrane and generating pores, they lyse midgut epithelial cells. Members of the 3-Domain Cry family are among the proteins utilized worldwide for pest control, and its mode of action has been studied in depth. Cry toxins attach to specific receptors on the host cell surface and are activated by host proteases after receptor binding, resulting in the creation of an insertion-competent pre-pore oligomeric structure. Cry toxins, on the other hand, interact directly with membrane lipids and intrude into the membrane.

The mechanism of action of three-domain crystal proteins has primarily been investigated in lepidopteran insects. The "classical" approach, the sequential binding model, and the signaling pathway model have all been proposed to describe the mode of action of three-domain Cry toxins. The "classical" model proposes that the toxin lyses the midgut epithelial cells of susceptible insects by going through the following steps: (a) Crystal inclusion ingestion and dissolution in the alkaline midgut lumen; (b) Protoxin (native protein) proteolytic activation, which converts the native Cry protein into smaller protease-resistant toxic polypeptides; (c) Binding of toxin fragments to specific receptors on the surface of the midgut. These holes cause epithelial cell lysis, resulting in midgut disorganisation and insect mortality. In addition, spores can colonise, germinate, and reproduce in the hemolymph, causing septicemia in the larvae. Although this system has been recognized for many years, some aspects (such as pore structure and pore assembly mechanism) are still unknown. According to the sequential binding model, Cry toxins bind to cadherin-like proteins (transmembrane glycoproteins that act as toxin receptors) and undergo a conformational change that favors proteolytic removal of the α-1 helix from domain I and formation of an oligomeric pre-pore structure after being activated by intestinal proteases.

Later, Binding to a secondary receptor, such as an aminopeptidase, allows the pre-pore structure to be inserted into the membrane more easily, resulting in cell and insect death. The signaling-pathway concept, on the other hand, posits that the harmful activity is mediated by specific binding to cadherin receptors, leading to undescribed Mg²⁺-dependent and Adenylyl Cyclase (AC) Protein Kinase A (PKA), Necrotic cell death is caused by a signaling mechanism. Both models, particularly the sequential binding model, are supported by little reliable experimental evidence, and the current available information supports the "classical" model postulating that Cry toxins act by forming pores, despite the fact that most events leading to their formation and receptor binding are still poorly understood. While cadherins and amino peptidases have been suggested as potential Cry toxin receptors, alpha amylases and alpha glycosidases, prohibitin, and Alkaline Phosphatases (ALP) have also been considered. The precise relevance of various putative receptors discovered for certain poison is still unknown.