Genomic changes in insect body resistance against insecticides

Introduction

The continuous struggle between humans and insect pests has relied heavily on synthetic insecticides as the principal means of pest management. However, the increasing occurrence of insecticide resistance, together with growing concerns regarding environmental degradation, biodiversity loss, and risks to human health, has challenged the long-term sustainability of this approach (Adam et al., 2024; Wan et al., 2025) [1,67] . Prolonged and often excessive application of insecticides has imposed intense selection pressure on insect populations, accelerating the evolution of resistant strains and creating serious challenges for modern agriculture, public health, and ecosystem stability. Insect pests cause substantial losses in agricultural crops, forests, stored products, and livestock feed, while numerous species act as vectors of viruses, bacteria, protozoa, and parasitic pathogens that threaten human and animal health (World Health Organization [WHO], 2024). Beyond direct crop damage, insect infestations compromise global food security, disrupt ecosystem functioning, and impose significant economic losses, particularly in low-and middle-income countries. Recent evidence suggests that climate change, agricultural intensification, and global trade are accelerating the spread, establishment, and persistence of insect pests by expanding their geographic distribution, increasing the number of generations per year, and enhancing their capacity to damage crops. Under a 2°C global warming scenario, insect pest-induced yield losses are projected to increase by approximately 46 per cent in wheat, 19 per cent in rice, and 31 per cent in maize compared with current levels, highlighting the escalating challenge of sustainable crop protection and global food security (Ma et al., 2025; FAO, 2025). Among the most destructive invasive pests, the tomato leaf miner (T. absoluta), native to South America, has spread to more than 100 countries across Europe, Africa, Asia, and the Middle East since its introduction. Under severe infestations, it can cause yield losses of up to 80-100% in tomato if left unmanaged, resulting in substantial economic damage and increased reliance on chemical insecticides. Moreover, the rapid evolution of resistance to multiple insecticide classes has further complicated its management, increased production costs and reducing the effectiveness of available control measures, thereby making T. absoluta one of the most economically important invasive agricultural pests worldwide (Desneux et al., 2010; Biondi et al., 2018) [13,24] . The global dependence on chemical insecticides remains substantial owing to their indispensable role in safeguarding agricultural productivity and public health. According to the latest FAOSTAT statistics, global agricultural pesticide use reached 3.73 million tonnes of active ingredients in 2023, representing a two-fold increase since 1990 despite a slight decline compared with 2022. Herbicides accounted for the largest share of pesticide consumption (51%), followed by insecticides (22%), fungicides and bactericides (22%), and other pesticide classes (5%). Brazil was the largest pesticide-consuming country (800.65 thousand tonnes), followed by the United States (429.50 thousand tonnes), Indonesia (294.94 thousand tonnes), Argentina (262.51 thousand tonnes), and China (229.03 thousand tonnes), while India ranked 17th globally with an estimated pesticide consumption of 40.09 thousand tonnes (FAO, 2025). Insecticides primarily disrupt essential physiological processes in insects, particularly neural transmission and cellular energy metabolism, and have contributed significantly to increased agricultural productivity since the Green Revolution. Several major classes of insecticides, including organophosphates, carbamates, pyrethroids, neonicotinoids, diamides, and spinosyns, have played a pivotal role in the management of agricultural and public health pests. However, their intensive and repeated use has imposed strong selection pressure on insect populations, resulting in the evolution of insecticide resistance in more than 600 arthropod species, with thousands of documented resistance records reported worldwide. Consequently, the efficacy of many conventional insecticides has declined substantially, posing a major threat to sustainable pest management, agricultural productivity, and global food security (Sparks & Nauen, 2015; Bass et al., 2015; Arthropod Pesticide Resistance Database [APRD], 2025) [12,48] . Insecticide resistance develops when heritable genetic changes reduce the susceptibility of pest populations, ultimately resulting in repeated control failures despite the correct application of insecticides according to recommended practices. The Insecticide Resistance Action Committee (IRAC, 2025) defines insecticide resistance as, "A heritable change in the sensitivity of a pest population that is reflected in the repeated failure of a product to achieve the expected level of control when used according to the label recommendation for that pest species."

The continued evolution of insecticide resistance has substantially reduced the efficacy of many conventional insecticides, making the management of economically important insect pests increasingly difficult. As resistance becomes more widespread, growers often respond by increasing application frequency, applying higher doses, or shifting to alternative insecticides, thereby intensifying selection pressure and accelerating the evolution of resistant populations. Excessive reliance on insecticides also contributes to environmental contamination, disrupts beneficial arthropods and biodiversity and poses risks to human and animal health. The evolution of resistance is driven by multiple biological and operational factors including pre-existing genetic variation, high reproductive capacity, short generation times, gene flow, and the repeated use of insecticides with the same mode of action, which promote the rapid selection and spread of resistanceconferring alleles within pest populations. Consequently, sustainable insecticide resistance management (IRM) strategies including insecticide rotation based on mode of action, integrated pest management (IPM), regular resistance monitoring and the development of innovative pest control approaches are essential to delay resistance evolution, preserve insecticide efficacy and ensure longterm agricultural productivity and environmental sustainability (IRAC, 2025; FAO, 2025; Bass and Field, 2025; Ma et al., 2025; Sparks et al., 2025) [11] . When these insects are exposed to an insecticide, the toxic compound penetrates their cuticle and is absorbed into their body. The insecticide then reaches its target site, such as the nervous system where it disrupts normal physiological functions, ultimately causing paralysis and death. This demonstrates the high effectiveness of insecticides against susceptible populations before resistance evolves.

Factors Responsible for development of Insecticide Resistance in field condition.

Resistance is driven by various factors, including genetic variability, high reproductive rates, and operational practices such as repeated use of similar chemical classes. These factors facilitate rapid selection of resistant phenotypes and increase the likelihood of resistance allele fixation within populations.

• 1. Biological Factors: Biological factors are generation time, number of offspring per generation migration and emigration insect species strongly affect their potential to develop and maintain insecticide resistance (Carriere et al., 2010) [16] .

• 2. Genetic Factors: Genetic factors are frequency and dominance of the resistance gene, fitness of resistance genotype and number of different resistance alleles. (Hawkins et al., 2019) [34] . • 3. Operational Factors: Treatment, persistence and insecticide chemistry, all of which may and therefore timing and dosage of insecticide application should be operational factors (Sparks et. al. 2021, Nauen, et.al. 2019) [48] . Low-dose insecticides application is a major cause of development of resistance (IRAC, International 60 th Meeting 2026). • 4. Management Practices: Management practices have a major impact on the development of insecticide resistance in agroecosystems (Thrall et al., 2011) [64] . Monoculture-based production systems create optimum conditions for pest outbreaks, leading to increased dependence on insecticides and increased selection pressure for resistance. [16, 34] . [21] (Mutero et al., 1994) [47] . (2) Physiological and metabolic targets (e.g., chitin synthase, ryanodine receptor, mitochondrial respiratory chain, etc.) (Hemingway et al., 2004), (Liu et al., 2011) [36,43] . (3) Growth and developmental targets (e.g., juvenile hormone receptors, ecdysteroid receptors, etc.) (Ononamadu et al.2021) [50] .

(4) Other novel or rare targets (e.g., octopamine receptor (Verlinden et.al 2010, Roeder T. 2020) [55,65] , midgut cell membranes (Wang, et.al. 2016) [68] , oxidative phosphorylation and decoupling agents, etc.) I. Voltage-gated sodium channels: Mutations in these channels can confer resistance to pyrethroids and DDT, a phenomenon known as "knockdown resistance" or "kdr". kdr (Knockdown Resistance) Mutations The term kdr refers to mutations in the voltage-gated sodium channel gene that confer resistance to pyrethroids and DDT. This mutation, such as L1014F in mosquitoes, alter the sodium channel structure, reducing the insecticide ability to induce paralysis and death of mosquitoes. kdr mutations are widespread in many insect species and are a major focus of resistance monitoring efforts (Ranson et al., 2000) [53] .

II. Acetylcholinesterase (AChE):

Changes in AChE can be preventing organophosphate and carbamate from effectively inhibiting this enzyme, leading to formation of resistance. Ace-1 Mutations in the ace-1 gene, which encodes acetylcholinesterase, are responsible for resistance to organophosphates and carbamates. The G119S mutation in Anopheles mosquitoes, for example, reduces the binding affinity of acetylcholinesterase, organophosphates diminishing to their effectiveness in controlling malaria vectors (Weill et al., 2003) [69] .

III. GABA receptors:

Mutations in GABA-gated chloride channels reduce susceptibility to cyclodiene insecticides (Remnant et. al., 2014, Gassel et. al., 2014) [28,54] . Target-site resistance occurs when mutations in the genes encoding the target proteins of insecticides reduce the chemical's ability to bind and exert its toxic effects. For example, mutation in the voltage-gated sodium channel gene is responsible for resistance to pyrethroids, a widely used class of insecticides. These mutations alter the structure of the sodium channel, preventing pyrethroids from disrupting nerve function (Davies et al., 2007) [21] .

Metabolic resistances

• Resistant insects may detoxify and destroy the toxin faster rate than susceptible insects, and quickly rid their bodies of the toxic molecule. • Most common mechanism and often presents the greatest challenge (Pu et al.,2024). • Insect use their internal enzyme systems to break down the insecticides. • Resistant strains may possess high levels or more efficient forms of this enzyme. • In addition to being more efficient, this enzyme system also may have a broad spectrum of activity (i.e., they can degrade many different insecticide). • The normal enzymatic metabolism of this insect is modified to increase insecticide detoxification or prevent activation of insecticides. • The enzymes responsible for detoxification of xenobiotics in living organisms are transcribed by members of large multigene families of esterases, oxidases, Glutathione transferases (GSTs) (Casida et al., 2017) [18] . • In Dipteran insects, they occur as a gene cluster on the same chromosome. Individual member of the gene clusters may be modified in instances of insecticide resistance, by changing a single amino acid that converts the specificity of an esterase to an insecticide hydrolase or by existing as multiple-gene copies that are amplified in resistant insects (the best studied examples are the B1 and A2-B2 amplicons in Culex pipien and C. quinque (Brogdon and McAllister, 1998) [15] .

Behavioural resistance

Behavioural resistance is one of the earliest adaptive mechanisms by which insects respond to insecticide exposure. It occurs when insects modify their behaviour to minimize or avoid contact with insecticides, thereby reducing exposure to toxic compounds without developing physiological or biochemical tolerance (Sparks et al., 1989; Lockwood et al., 1984) [44] .

• Resistant insect may detect or recognize a danger and avoid the toxin (Lockwood et al., 1984; Sparks et al., 1989) [44] . • This mechanism of resistance has been reported for various classes of insecticides, including organochlorine, organophosphate, carbamate and pyrethroid (Sparks et al., 1989; Georghiou et al., 1990) [29] . • Insects may simply stop feeding if they come across certain insecticide, or leave the area where spraying occurred (for instance, they may move to the underside of a sprayed leaf, move deeper in the crop canopy or fly away from the targeted area) (Hoy et al., 1998; Sparks et al., 1989) [37] . • E.g. Plutella xylostella (Diamond back moth): Reduced oviposition on sprayed crops (Talekar and Shelton, 1993; Furlong et al., 2013) [27,62] .

Penetration resistance

• Resistant insects may absorb the toxin slower than susceptible insect (Oppenoorth et al., 1985; Feyereisen et al., 2015) [26,51] . • Penetration resistance occurs when the insect's outer cuticle develops barriers which can slow absorption of the chemical into their body (Bass and Field, 2025; Balabanidou et al., 2018) [10,11] . • This can protect insects from a wide range of insecticides (Balabanidou et al., 2018; Feyereisen, 2015) [10,26] . • Penetration resistance is frequently present among the other forms of resistance, and reduced penetration intensifies the effects of those other mechanisms (Sparks and Nauen, 2015; Balabanidou et al., 2018) [10,48] . • Helicoverpa armigera: Reduced deltamethrin penetration through enhanced cuticular esterases (Ahmad et al., 2006) [2] .

Cross-resistance and multiple resistance:

While not a standalone mechanism, cross-resistance and multiple resistance amplify the challenges posed by resistance.

Cross-resistance:

Occurs when a single resistance mechanism provides tolerance to multiple pesticides with similar modes of action. For example, enhanced cytochrome P450 activity can confer resistance to both organophosphates and pyrethroids. (Hall et al., 1994, Quintela, et. al., 2025, Thiesen, et.al. 2025) [33] Multiple resistance: Occurs when a pest population exhibits more than one resistance mechanism, making it resistant to multiple classes of pesticides. (Tang et al. 2025; Kiuru et al. 2025) [40] Impacts of insecticide resistance in Agriculture -• Increased pest population • Increased costs for farmers (Bass et al., 2015) [12] .

• Threat to food security (Wan et al., 2025) [67] .

• Loss of profitability (Ali et al., 2023) [4] • Reduce Effectiveness of Control measures (Sparks and Nauen, 2015) [48] . • Pest resurgence and secondary pest outbreak (Guedes et al., 2016) [31] • Higher pesticide residues in agricultural products (Carvalho, 2006) [17] . • Environmental Pollution (Gill et al., 2014; Aktar et al., 2009) [3,30] . • Destruction of natural enemies (Chagnon et al., 2015; Desneux et al., 2007) [19,22] . • Human and Animal Health risks (Carvalho et al., 2006) [17] . • Reduce crop yield and quality • Development of cross resistance (Mir Washim et. al.

2024) [46] 6 [39,66] . Therefore, modern pest management strategies emphasize integrated pest management approaches that combine biological, chemical, and ecological tactics to delay development of resistance evolution and minimize ecological impacts. 1. Integrated Pest Management (IPM) (Desneux et al., 2022). [22] ). 2. Rotation and combination of pesticides (Zhao et al., 2010; Sparks et al., 2020) [71] . 3. Sequential Application Strategies (Sarwar et al., 2015) [56] 4. Use of biopesticides (Ngegba et al.,2022) [49] 5. Role of biological control (Haase et [9,32,42] . 6. Adoption of Genetically Modified (GM) crops (Kumar et al., 2008) [41] . 7. Host Plant Resistance / use of resistance plant varieties (Dara, 2022) [20] . 8. Epigenetic Regulation of Insecticide Resistance (Biswas, 2025) [14] 9. Use of recommended insecticide doses and proper application practices (Sparks et al., 2020; Nauen et al., 2022) [48] . 10. Conservation of natural enemies (Desneux et al., 2022) [22] . [38,70] . [20] . • Expansion of biological control and biopesticides (Lacey et al., 2022) [42] . • Climate-smart pest management approaches (Deutsch et al., 2018) [25] .

Future Strategies

Conclusion

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