Bt Research 2025, Vol.16, No.5, 182-193 http://microbescipublisher.com/index.php/bt 188 usually acts as a transcriptional repressor, suppressing numerous targets including virulence genes. In the late stage of growth, the rise of Spo0A inhibits AbrB, causing many previously repressed genes to begin expression (Lin and Xu, 2024). Another type of global regulatory factor is stress-responsive. For example, the σ^B factor is activated under stress such as oxidation and osmosis. σ^B will induce the expression of some protective genes (such as oocyte-laying, repair enzymes, etc.), and may also affect the time of spores and toxin production. When the insect's internal environment poses a stress on Bt, the activation of these global factors helps Bt overcome the difficulties and complete the infection process. 5.3 Dynamic response of environmental adaptation and metabolic pathways The environment in which Bt is located is changing rapidly, from laboratory culture medium to field leaves surfaces to insect intestines, the physical and chemical conditions vary greatly. The ability of Bt to successfully cause disease is inseparable from its dynamic response to environmental changes in metabolic pathways. In the insect gut, Bt encounters environmental challenges of alkaline, high concentrations of enzymes and complex microbiota. A study on corn borer larvae showed that after Bt enters the intestine, it triggers dynamic changes in the composition of the insect's midgut microbiome and increases the total bacterial volume. When insects lose gut symbionts, their sensitivity to Bt toxins is actually significantly improved. This shows that the metabolic activity of Bt in the intestine may interact with the intestinal microbiota (Li et al., 2020). When Bt is metabolized vigorously, it can suppress certain beneficial bacteria, thereby weakening insect resistance to Bt. This is an environmental-metabolic-virulence chain reaction. In addition, Bt also has a metabolic response mechanism for environmental parameters such as temperature. Different Bt strains have different adaptations to temperature changes. An experiment compared the virulence of Bt israelensis (mosquitoicidal strain) to Aedes larvae at different temperatures, and found that high-temperature culture can induce Bt to produce more melanin, thereby enhancing the spores' anti-ultraviolet and high-temperature ability and indirectly improving the mosquito-killing effectiveness in fields (Cao et al., 2018). This shows that Bt can adapt to fluctuations in ambient temperature and other factors by changing secondary metabolism (such as pigment synthesis). 6 Metabolic Pathways Interact with Insect Intestinal Environment 6.1 The survival and adaptation mechanism of Bt in the intestines of insects The insect midgut is the main place where Bt works and is also a challenging living environment. After Bt spores and crystals enter the insect's midgut with feeding, they first face the effects of strong alkaline pH and digestive enzymes. For Bt vegetative cells, the environment around pH 10 is not friendly. Bt needs to adapt to high pH as soon as possible in the intestines of insects to germinate spores and reproduce vegetative cells, thereby assisting in infection (Peng et al., 2024). In addition to pH, there are also a variety of antibacterial substances (such as antibacterial peptides, lysozymes) and complex symbiotic bacteria in the intestines, which put pressure on Bt colonization. When Bt enters the insect intestine, it uses metabolic pathways to enhance its own defense and competitiveness (Grizanova et al., 2022). In the insect intestine, the metabolic activity of Bt is also reflected in chemotaxis and colonization. Bt may use flagellar movement and chemotaxis to gather in areas that are prone to colonization in the intestine (such as the posterior part of the midgut). In addition, Bt-germinated spore cells adhere to the midgut surface, which requires the formation of adhesion factors and biofilm. 6.2 Interaction between intestinal pH, enzyme and Bt metabolism The high alkalinity of the insect midgut environment and various digestive enzymes are not only a necessary condition for the Bt toxin to play a role, but also a severe test for Bt bacteria. There is actually an interaction and balance between Bt and this environmental factor. The midgut pH ~10 is conducive to the rapid dissolution of Bt-spore crystals to explain the release of protoxins, but excessive pH may also affect the stability and receptor binding of toxins (Liu et al., 2020). Bt adopts two strategies in evolution, on the one hand, its Cry toxin structure is required for activation at high pH, but if the pH continues to rise to extremes (>11), the toxin activity may be reduced. Secondly, midgut digestive enzymes (such as trypsin, chymotrypsin, etc.) have both activation and potential destructive effects on Bt toxins.
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