Bt Research 2025, Vol.16, No.6, 234-241 http://microbescipublisher.com/index.php/bt 234 Review Article Open Access Overcoming Insect Resistance to Bt Toxins: Strategies and Innovations Jia Xing 1, Wenzhong Huang 2 1 Tropical Animal Resources Research Center, Hainan Institute of Tropical Agricultural Resources, Sanya, 572025, Hainan, China 2 Biomass Research Center, Hainan Institute of Tropical Agricultural Resouces, Sanya, 572025, Hainan, China Corresponding email: wenzhong.huang@hitar.org Bt Research, 2025, Vol.16, No.6 doi: 10.5376/bt.2025.16.0026 Received: 05 Sep., 2025 Accepted: 10 Oct., 2025 Published: 18 Nov., 2025 Copyright © 2025 Xing and Huang, This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Preferred citation for this article: Xing J., and Huang W.Z., 2025, Overcoming insect resistance to Bt toxins: strategies and innovations, Bt Research, 16(6): 234-241 (doi: 10.5376/bt.2025.16.0026) Abstract Bacillus thuringiensis (Bt) toxin, which is widely used in genetically modified crops, has significantly reduced pest damage and the use of chemical pesticides worldwide. However, the rapid evolution of insect resistance to Bt toxins has become the main obstacle restricting the sustainability of Bt technology, seriously threatening the long-term stability of the integrated pest management system. This study systematically reviews the currently revealed resistance mechanisms, including receptor gene mutations, enhanced detoxification metabolic pathways, and behavioral adaptations, discusses field population resistance monitoring methods and resistance evolution dynamics, and summarizes multiple molecular and biotechnological strategies for overcoming resistance. This includes the "gene pyramid" technology of superimposing multiple Bt genes, the combined use of Bt toxins and RNA interference (RNAi) to enhance insecticidal effects, and the use of gene editing tools such as CRISPR to target and destroy genes related to insect resistance. By analyzing typical cases from the United States, China, India and other places, this study evaluated the successful experiences and failure reasons of resistance management strategies, highlighting the importance of comprehensive governance and scientific supervision. This research holds significant theoretical and practical value for extending the effective lifespan of Bt crops, reducing pesticide dependence, and promoting the construction of a green agricultural system. Keywords Bt toxin; Resistance mechanism; Gene pyramid technology; RNA interference; Resistance management strategy 1 Introduction In the mid-1990s, Bt crops were officially launched on the market. Since then, Cry proteins, especially the type secreted by Bacillus thuringiensis (Bt), have appeared more and more frequently in cotton, corn and soybeans. These crops rely on the Bt toxins they express to deal with the stubborn Lepidoptera and Coleoptera pests in the fields, indeed saving a lot of trouble with chemical pesticides. The second-generation Bt crops composed of multiple Cry proteins have also been used to deal with a wider range of pest populations while delaying the emergence of resistance (Tabashnik, 2015). They not only increased crop yields, but also demonstrated obvious advantages in environmental protection and pesticide reduction. In addition, Bt toxins have a relatively small impact on non-target organisms, and they have become an indispensable part of the global integrated Pest management (IPM) system. However, to be fair, this "pest control tool" of Bt crops is not without flaws. As time went by, some insects gradually "figured out the tricks" of Bt toxins. In many countries, it has been confirmed that several pest varieties have developed resistance to Bt. This situation has been particularly prominent in the past two decades, especially in crops that express only one Cry protein (Jurat-Fuentes et al., 2021). Where is the problem? At present, resistance may be related to receptor mutations (such as cadherin, ABC transporter). Some studies have also found that changes in proteases affecting toxin activation and alterations in midgut structure may play a certain role (Soberon et al., 2007; Tay et al., 2015; Badran et al., 2016). Particularly worthy of attention are the mutations of ABC transporters such as ABCA2, which are highly correlated with the resistance of pests like cotton bollworms to Cry2Ab toxins, indicating that the resistance mechanism may be more complex than expected. Although the multi-toxin expression strategy has achieved certain effects in delaying resistance, some field resistance phenomena still persist. This also reminds us that the resistance issue cannot be ignored, and continuous monitoring and dynamic management are imperative.
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