Bt Research 2025, Vol.16, No.6, 234-241 http://microbescipublisher.com/index.php/bt 240 If we truly want to take control of this situation in the future, we may have to rely more on the integration of multiple disciplines. Protein engineering can help us quickly produce new Bt toxins and enhance their ability to resist variant receptors. Meanwhile, finding breakthroughs from hormone signals and the relationship between pests and hosts may also bring about new target resources. From a broad perspective, the sustainability of pest management does not only rely on technological upgrades, but also on detailed management regulations, farmer training and policy coordination - in other words, while laboratories should take the lead, the coordination at the field level should not be neglected. Only by truly integrating biotechnology, ecological thinking and socio-economic factors can Bt crops possibly gain a firm foothold in the long term and replace more traditional chemical control roles. Acknowledgments Thank you to Dr. Zhang for his technical support in data analysis and visualization, and also thank the members of the research team for their discussions and suggestions during the paper writing. Conflict of Interest Disclosure The authors affirms that this research was conducted without any commercial or financial relationships that could be construed as a potential conflict of interest. References Badran A., Guzov V., Huai Q., Kemp M., Vishwanath P., Kain W., Nance A., Evdokimov A., Moshiri F., Turner K., Wang P., Malvar T., and Liu D., 2016, Continuous evolution of B. thuringiensis toxins overcomes insect resistance, Nature, 533: 58-63. https://doi.org/10.1038/nature17938 Blanquart F., 2019, Evolutionary epidemiology models to predict the dynamics of antibiotic resistance, Evolutionary Applications, 12: 365-383. https://doi.org/10.1111/eva.12753 Furusawa C., Horinouchi T., and Maeda T., 2018, Toward prediction and control of antibiotic-resistance evolution, Current Opinion in Biotechnology, 54: 45-49. https://doi.org/10.1016/j.copbio.2018.01.026 Guo Z., Kang S., Sun D., Gong L., Zhou J., Qin J., Guo L., Zhu L., Bai Y., Ye F., Wu Q., Wang S., Crickmore N., Zhou X., and Zhang Y., 2020, MAPK-dependent hormonal signaling plasticity contributes to overcoming Bacillus thuringiensis toxin action in an insect host, Nature Communications, 11: 1-14. https://doi.org/10.1038/s41467-020-16608-8 Gupta M., Kumar H., and Kaur S., 2021, Vegetative insecticidal protein (Vip): a potential contender from Bacillus thuringiensis for efficient management of various detrimental agricultural pests, Frontiers in Microbiology, 12: 659736. https://doi.org/10.3389/fmicb.2021.659736 Hu D., Wang D., Pan H., and Liu X., 2025, Molecular mechanisms underlying resistance to Bacillus thuringiensis cry toxins in lepidopteran pests: an updated research perspective, Agronomy, 15(1): 155. https://doi.org/10.3390/agronomy15010155 Hughes D., and Andersson D., 2017, Evolutionary trajectories to antibiotic resistance, Annual Review of Microbiology, 71: 579-596. https://doi.org/10.1146/annurev-micro-090816-093813 Jurat-Fuentes J., Heckel D., and FerréJ., 2021, Mechanisms of resistance to insecticidal proteins from Bacillus thuringiensis, Annual Review of Entomology, 66: 121-140. https://doi.org/10.1146/annurev-ento-052620-073348 Khudhair I., Abbood N., and El-Amier Y., 2025, Insecticide resistance in agricultural pests: mechanisms case studies and future directions, University of Thi-Qar Journal of Science, 12(1): 245-250. https://doi.org/10.32792/utq/utjsci/v12i1.1381 Li W., Zhang H., Assaraf Y., Zhao K., Xu X., Xie J., Yang D., and Chen Z., 2016, Overcoming ABC transporter-mediated multidrug resistance: molecular mechanisms and novel therapeutic drug strategies, Drug Resistance Updates : Reviews and Commentaries in Antimicrobial and Anticancer Chemotherapy, 27: 14-29. https://doi.org/10.1016/j.drup.2016.05.001 Liu L., Xu P., Liu K., Wei W., Chang Z., and Cheng D., 2022, Advances in receptor-mediated resistance mechanisms of Lepidopteran insects to Bacillus thuringiensis toxin, Chinese Journal of Biotechnology, 38(5): 1809-1823. https://doi.org/10.13345/j.cjb.210834 Pacheco S., Cantón E., Zúñiga-Navarrete F., Pecorari F., Bravo A., and Soberón M., 2015, Improvement and efficient display of Bacillus thuringiensis toxins on M13 phages and ribosomes, AMB Express, 5: 73. https://doi.org/10.1186/s13568-015-0160-1
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