Bt Research 2025, Vol.16, No.5, 182-193 http://microbescipublisher.com/index.php/bt 187 competitive bacteria or defensive symbiotic bacteria in the insect intestines, thereby allowing itself or harmful bacteria to reproduce faster and spread to the blood cavity to cause septic infection. Small molecule toxins in Bt metabolites such as sulvionin (β-exotoxin) can be absorbed by insects and poison the tissues throughout the body, accelerating insect death. Finally, Bt secondary metabolites may also interfere with insects’ immune systems. For example, some lipopeptide antibiotics can not only kill bacteria, but also induce or deplete immune responses in insects, making it more difficult to remove invading Bt (Hrithik et al., 2022). 4.3 Control of secondary products by metabolic regulatory network The synthesis of Bt secondary metabolites often occurs during secondary growth stages or under stress conditions, and its regulation involves complex metabolic networks and signaling pathways. Generally speaking, when Bt transitions from the exponential growth phase to the stable phase, global metabolic regulation changes, and only then is the secondary metabolic pathway released and inhibited and expressed (Xu, 2024). Only when the carbon and nitrogen source decrease to a certain extent and these inhibitory effects weaken will Bt begin to synthesize large quantities of secondary products such as antibiotics and enzymes. This mechanism can be regarded as a distribution strategy between survival priority and competitive suboptimal. It does not waste resources when growing vigorously, but only uses "chemical weapons" when nutrition is scarce and needs to compete for ecological niches. There are often some specific regulatory genes in the Bt genome that regulate the synthesis of secondary metabolites, such as encoding LysR family regulators or σ^H, which co-regulate multiple secondary metabolic gene clusters (Yi et al., 2020). In addition, the population sensing system of Bt may also be involved in regulating the production components of secondary metabolites. Although Gram-positive bacteria usually use cyclic oligopeptides for population sensing, the possibility of enzyme catalyzing the synthesis of gamma-butyrolactone signaling molecules has also been found in some of the genomes of Bt. 5 Signal Transduction and Metabolic Regulation 5.1 The role of metabolites as signaling molecules Bt cells not only use metabolites as nutrients and energy, but also treat them as information molecules to perceive environmental changes and adjust physiological behavior. A typical example is the role of small molecule metabolites in population sensing and feedback regulation. For Gram-positive bacteria, cyclic peptides are often used as quorum sensing signals, but recent studies have suggested that some metabolites themselves can act as signal molecules. The lactic acid accumulated by Bt in an alkaline environment is not only used to neutralize pH, but may also enable the expression of the corresponding gene by regulating transcription factor LldR or CRP/FNR family regulatory proteins (Peng et al., 2024). Peng et al. (2024) found that the lactic acid metabolism pathway induced by Bt under alkaline stress is controlled by a regulator called LtmR, which is very sensitive to changes in lactic acid concentration. When lactic acid accumulates, LtmR will feedback inhibit certain metabolic genes, prompting the bacteria to temporarily suspend energy metabolism and strengthen the alkali resistance mechanism. Bt may also use these metabolite concentration ratios to determine whether the host environment is nutritious or poor, thereby deciding whether to maintain growth or initiate sporotoxin synthesis. 5.2 Regulation of metabolic pathways by global transcription factors There are a variety of global transcription factors in Bt, which can convert metabolic status into gene expression regulation, and have an important impact on bacterial virility. One of these is nutritionally responsive transcription factors, such as CodY, CcpA, AbrB, etc. CodY senses the levels of GTP and branched chain amino acids in cells, binds these molecules when nutrients are abundant and acts as transcriptional repressors, shutting down many spore production and virulence-related genes; when nutrients decrease, CodY loses the effect and the related genes are expressed. This mechanism has been demonstrated in Bacillus subtilis and is also believed to exist and regulate the production of crystal toxins and enzymes in Bt (Mei et al., 2016). CcpA is responsible for carbon metabolism repression. When there is sufficient glucose, CcpA actively inhibits the genes of secondary metabolic enzymes. AbrB is a transition phase regulatory protein that is abundant in the exponential growth phase and
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