Isaac Ishaaya

Biochemical sites of insecticide action and resistance

Biochemical Processes Related to Insecticide Action: an Overview.- 1 Introduction.- 2 Chitin Synthesis Inhibition.- 3 Ecdysone and Juvenile Hormone Receptors.- 4 Acetylcholine Receptors.- 5 GABA and Glutamate Receptors and Ion Channels.- 6 Other Biochemical Sites.- 7 Conclusions.- References.- GABA and Glutamate Receptors as Biochemical Sites for Insecticide Action.- 1 Introduction.- 2 GABA Receptors in Mammals and Insects.- 2.1 Classification of GABA Receptors.- 2.2 Structure and Physiological Role of Insect GABA Receptors.- 2.3 Pharmacology of GABA Receptors.- 3 Summary of Effects of Convulsants and Avermectins on the GABA Receptor.- 3.1 Polychlorocycloalkanes and Related Norbornanes.- 3.2 Picrodendrin and Silphinene Natural Products.- 3.3 Fipronil and Fipronil Analogs.- 3.4 Trioxabicyclooctanes and Related Compounds.- 3.5 New Avermectins and the Mammalian GABA Receptor.- 3.6 Altered GABA Receptors in Resistance.- 3.7 Resistance to New and Experimental Insecticides.- 4 Glutamate-Gated Chloride Channels.- 4.1 Physiology, Pharmacology, and Molecular Structure.- 4.2 Effects of the Avermectins.- 4.3 New Avermectins and Their Uses.- 4.4 Target Site Resistance to the Avermectins.- 5 Conclusions.- References.- Insecticides Affecting Voltage-Gated Ion Channels.- 1 Insecticides and Ion Channels.- 1.1 Scope and Aim.- 1.2 Voltage-Gated Ion Channels.- 2 Industrial Insecticides Targeting Ion Channels.- 2.1 Insecticides of the Voltage-Gated Sodium Channels.- 2.2 Insecticides of the Potassium and Calcium Channels.- 3 The Functional Diversity of Insecticides.- 3.1 Multiplicity of Effects.- 3.2 Distinction Between Mammals and Insects.- 4 Neurotoxic Polypeptides.- 4.1 Animal Group Specificity.- 4.2 Insect-Selective Neurotoxins Affecting the Voltage-Gated Sodium Channels.- 4.2.1 Scorpion Venom Toxins.- 4.2.2 Spider Venom Toxins.- 4.3 Insect-Selective Neurotoxins Affecting the Voltage-Gated Calcium Channel.- 5 Recombinant Baculovirus Bioinsecticides.- 6 Allosteric Coupling and Allosteric Antagonism.- References.- Acetylcholine Receptors as Sites for Developing Neonicotinoid Insecticides.- 1 Introduction.- 2 Insect Nicotinic Acetylcholine Receptors.- 2.1 Structure.- 2.2 Diversity.- 3 Compounds Acting on the Nicotinic Acetylcholine Receptor.- 3.1 Radioligand Binding Studies.- 3.2 Neonicotinoids.- 3.2.1 Imidacloprid and Related Structures.- 3.2.2 Mannich Adducts as Experimental Pro-Neonicotinoids.- 4 Electrophysiological Considerations.- 4.1 Whole Cell Voltage Clamp of Native Neuron Preparations.- 4.1.1 Correlation Between Electrophysiology and Radioligand Binding Studies.- 4.2 Agonists vs. Antagonists.- 4.3 Receptor Subtypes in Locusta migratoria.- References.- Ecdysteroid and Juvenile Hormone Receptors: Properties and Importance in Developing Novel Insecticides.- 1 Introduction.- 2 Ecdysteroids.- 2.1 Biology, Endocrinology and Molecular Biology.- 2.2 Receptors and Other Target Sites.- 2.3 Non-Steroidal Ecdysone Analogs and Their Mode of Action.- 2.4 Receptor-Based Screening Assays.- 2.5 Future Directions.- 3 Juvenile Hormone.- 3.1 Biology, Endocrinology and Molecular Biology.- 3.2 Receptors and Other Target Sites.- 3.3 JH Analogs and Their Modes of Action.- 3.4 Receptor-Based Screening Assays.- 3.5 Future Directions.- References.- Imaginal Discs and Tissue Cultures as Targets for Insecticide Action.- 1 Introduction.- 2 Imaginal Discs as Targets of Insect Hormones in Vivo and in Vitro.- 3 Insecticide Action in Vitro: Juvenile Hormone Mimics.- 4 Insecticide Action in Vitro: Chitin Synthesis Inhibitors.- 4.1 Organ Cultures.- 4.2 Cell Lines.- 5 Insecticide Action in Vitro: Ecdysteroid Agonists.- 5.1 Organ Cultures.- 5.2 Cell Lines.- References.- Insect Neuropeptide Antagonists: a Novel Approach for Insect Control.- 1 Introduction.- 2 Backbone Cyclic Neuropeptide-Based Antagonist (BBC-NBA) Approach.- 2.1 Determination of the Active Sequence in the Neuropeptide.- 2.2 Development of a Competitive Lead Antagonist.- 2.3 Improvement of the Antagonistic Activity by Conformational Constraint.- 2.4 Backbone Cyclization: a Tool for Imposing Conformational Constraint on Peptides.- 2.5 Cycloscan: Conformationally Constrained BBC Peptide Libraries.- 3 Pheromone Biosynthesis Activating Neuropeptide.- 4 Implementation of the BBC-NBA Strategy to the Pyrokinin/PBAN Family.- 5 Conversion of Neuropeptide Antagonists into Insecticide Prototypes.- 6 Concluding Remarks.- References.- Ion Balance in the Lepidopteran Midgut and Insecticidal Action of Bacillus thuringiensis.- 1 Introduction.- 2 Pathogenesis.- 3 Dependence of Host and Pathogen on Midgut pH.- 4 Midgut K+ and H+ Regulation.- 4.1 The K+ Pump.- 4.2 The 2K+/1ATP Model for Midgut Alkalization.- 4.3 The 1K+/1ATP Model for Midgut Alkalization.- 4.4 Transmembrane and Transepithelial Ion Gradients.- 5 Disruption of Midgut Ion Homeostasis by Bacillus thuringiensis.- 5.1 In Vivo Changes.- 5.2 In Vitro Changes.- 5.3 What is the Source of the Elevated Hemolymph K+?.- 5.4 Larval Paralysis and Mortality Factors.- 5.5 ?-Endotoxin Effects on K+-Dependent Uptake of Amino Acids.- 5.6 Correlating ?-Endotoxin Effects on the Isolated Midgut with Insecticidal Activity.- 6 Receptor Binding and Ion-Channel Formation.- 6.1 Receptor Binding.- 6.2 Ion-Channel Formation in Artificial Membranes and BBMVs.- 6.3 Insect Cell Lines as Proxies for Midgut Cells In Vivo.- 7 Membrane Insertion and Pore Formation.- 8 Conclusions and Thoughts.- References.- Evolution of Amplified Esterase Genes as a Mode of Insecticide Resistance In Aphids.- 1 Introduction.- 2 Biochemistry of Esterase-Based Resistance in M. persicae.- 3 Molecular Genetics of Esterase Overproduction.- 3.1 Esterase Genes in Susceptible Aphids.- 3.Organization of Amplified Esterase Genes.- 3.3 Cytogenetic Studies of Amplified Esterases.- 4 Expression of Esterase Genes.- 5 Wider Implications.- References.- Insensitive Acetylcholinesterase as Sites for Resistance to Organophosphates and Carbamates in Insects: Insensitive Acetylcholinesterase Confers Resistance in Lepidoptera.- 1 Introduction.- 2 Acetylcholinesterase as a Resistance Mechanism.- 3 Insensitive AChE in Lepidopteran Species.- 4 Insensitive AChE in H. punctigera.- 5 Forms of AChE in Lepidoptera.- 6 Effects of Altered AChE on Acetylcholine Hydrolysis.- 7 Inhibition Ratios and Toxicity in Lepidoptera.- 8 Cross Resistance Between Organophosphates and Carbamates in Lepidoptera.- 9 Genetics of Resistance in Lepidoptera.- 10 Fitness of Resistance in Lepidoptera.- 11 Evolution.- 12 Control of Altered AChE in Lepidoptera.- 13 Population Genetics and Monitoring.- 14 Conclusions.- References.- Glutathione S-Transferases and Insect Resistance to Insecticides.- 1 Introduction.- 2 General Features of Glutathione S-Transferases (GSTs).- 2.1 Roles.- 2.2 Biochemical and Physiological Characteristics.- 2.3 Structure, Regulation, and Evolution of GST Genes.- 3 Insect GSTs.- 3.1 Roles.- 3.2 Biochemical and Physiological Characteristics.- 3.3 GSTs and Insecticide Resistance.- 3.4 Molecular Biology Studies.- 4 GST Studies of Several Insects.- 4.1 Drosophila melanogaster.- 4.2 Musca domestica.- 4.3 Anopheles gambiae.- 4.4 Plutella xylostella.- 5 Concluding Remarks.- References.- Cytochrome P450 Monooxygenases and Insecticide Resistance: Lessons from CYP6D.- 1 Cytochrome P450 Monooxygenases.- 2 Insecticide Resistance.- 3 Monooxygenase-Mediated Insecticide Resistance.- 4 CYP6D1 and Insecticide Resistance.- 5 Summary of the Lessons Learned from CYP6D1.- References.- Mechanisms of Organophosphate Resistance in Insects.- 1 Introduction.- 2 Physiological Mechanisms of Resistance.- 2.1 Resistance Mechanisms Involving Enhanced Biotransformation.- 2.1.1 Cytochrome-P450-Dependent Monooxygenases.- 2.1.2 Glutathione S-Transferases.- 2.1.3 Hydrolytic Enzymes.- 2.1.3.1 Quantitative Changes (Gene Amplification).- 2.1.3.2 Qualitative Changes.- 2.2 Target Site Insensitivity.- 2.3 Interactions Between Resistance Mechanisms.- 3 Summary.- References.- Insect Midgut as a Site for Insecticide Detoxification and Resistance.- 1 Introduction.- 2 The Insect Gut: a Natural Digestive-Absorption Architecture.- 3 Enzymatic Metabolism of Pesticide Involved in Resistance.- 4 Impact of Ingestion, and Penetration and Disposition in the Insect Body on Resistance to Pesticides.- 5 Attempts for Chemical Modeling of Digestion and Absorption in Insect Midgut.- 6 In Vitro Gut Cultures for Insecticidal Activity Studies.- References.- Impact of Insecticide Resistance Mechanisms on Management Strategies.- 1 Introduction.- 2 Overview of Resistance Mechanisms.- 3 Overview of Resistance Management Tactics.- 4 Diagnosing Resistance.- 4.1 In Vitro Assays for Diagnosing Resistance.- 5 Overpowering Resistance Mechanisms.- 6 Resolving and Exploiting Cross-Resistance.- 7 Conclusions.- References.

Biotype Q ofBemisia tabaci identified in Israel

The biotype status of samples of the whiteflyBemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) collected from several field and greenhouse sites in Israel during 1999–2000 was determined by polyacrylamide gel electrophoresis (PAGE) for general esterases, and by RAPD-PCR using primers of arbitrary sequence. Results of this survey provide the first published evidence for the occurrence of theB. tabaci Q biotype, alongside the more widely distributed B biotype. Based on the collected samples, it appears that both the B and Q biotypes are present in Israel, and that field populations consist of a mixture of the two biotypes. A possible link betweenB. tabaci biotypes and insecticide resistance is discussed.

Insecticides with Novel Modes of Action: An Overview

Conventional insecticides such as chlorinated hydrocarbons, organophosphates, carbamates and pyrethroids were successful in controlling insect pests during the past five decades, minimizing thereby losses in agricultural yields. Unfortunately, many of these chemicals are harmful to man and beneficial organisms and cause ecological disturbances. Although considerable efforts have been made to minimize the adverse environmental impact of pesticides and to maximize food production and health of the human population and domestic animals, there is today a great demand for safer and more selective insecticides affecting specifically harmful pests, while sparing beneficial insect species and other organisms. Furthermore, the rapidly developing resistance to conventional insecticides provides the impetus to study new alternatives and more ecologically acceptable methods of insect control as part of integrated pest management (IPM) programs.

Insecticides design using advanced technologies

Nanosuspensions: Emerging Novel Agrochemical Formulations.- Pharmacokinetics: Computational Versus Experimental Approaches to Optimize Insecticidal Chemistry.- High-Throughput Screening and Insect Genomics for New Insecticide Leads.- Transgenic and Paratransgenic Insects in Crop Protection.- Future Insecticides Targeting Genes Involved in the Regulation of Molting and Metamorphosis.- Trypsin Modulating Oostatic Factor for Developing Resistant Crops.- Nicotinic Acetylcholine Receptors as a Continuous Source for Rational Insecticides.- Mitochondrial Electron Transport Complexes as Biochemical Target Sites for Insecticides and Acaricids.- Inhibition of Programmed Cell Death by Baculoviruses: Potential in Pest-Management Strategies.- Plant Natural Products as a Source for Developing Environmentally Acceptable Insecticides.- Essential Oils as Biorational Insecticides-Potency and Mode of Action.- Insect Cell Lines as Tools in Insecticide Mode of Action Research.

Managing resistance to the insect growth regulator, pyriproxyfen, in Bemisia tabaci

The insect growth regulator pyriproxyfen (a juvenoid) effectively inhibits the hatching of eggs of the tobacco or cotton whitefly, Bemisia tabaci, as well as causing pupal mortality. Since 1991, this insecticide has been one of the main agents for controlling B tabaci on Israeli cotton. Seasonal trends of susceptibility to pyriproxyfen in field populations were monitored from June (prior to treatment) through late summer at different locations in Israel. After seven years of pyriproxyfen use within an insecticide resistance management strategy that limits this insecticide to a single application per season, susceptibility has been maintained in many areas. In other locations where pyriproxyfen had been used against geographically isolated populations of B tabaci, moderate to high levels of resistance have been observed. Ecological and agronomic factors that may contribute to geographical variation in selection for resistance are discussed. The dynamics of pyriproxyfen-susceptible and -resistant populations of B tabaci following a single application of pyriproxyfen were investigated under simulated field conditions in the laboratory. The susceptible population was suppressed very effectively, whereas effects of pyriproxyfen against the resistant population were much more transient. Differences in the productivity of susceptible and resistant strains in the absence of pyriproxyfen treatment could reflect a fitness cost accounting for observed reductions in resistance levels between seasons in the field. They may also explain why, following a recent reduction in the use of pyriproxyfen in cotton fields, resistance in 1998 declined to levels observed in 1995/6.

Dynamics of biotypes B and Q of the whitefly Bemisia tabaci and its impact on insecticide resistance

BACKGROUND The whitefly Bemisia tabaci (Gennadius) (Hemiptera: Aleyrodidae) is a key pest in many agricultural crops, including vegetables, ornamentals and field crops. B. tabaci is known for its genetic diversity, which is expressed in a complex of biotypes or, as recently suggested, a complex of distinct cryptic species. The biotypes are largely differentiated on the basis of biochemical or molecular polymorphism and differ in characteristics such as host plant range, attraction by natural enemies, secondary symbionts and expression of insecticide resistance. An extensive survey of B. tabaci biotypes and their impact on insecticide resistance was conducted from 2003 to 2012 in cotton fields and other crops from several locations in Israel. RESULTS Two biotypes of B. tabaci, B and Q, were identified, and some differences in the biotype dynamics were recorded from different areas. In northern Israel from 2003 to 2007, a higher proportion of the B biotype was consistently found in early season. However, by the end of the season a definite rise of the Q biotype was sampled, ranging from 60 to 100%, along with high resistance to the insect growth regulator (IGR) pyriproxyfen and to a lesser extent to the neonicotinoid insecticides. In fields located in the central part of Israel, the Q biotype was predominant throughout the seasons, with high resistance to pyriproxyfen. Since 2009, a significant shift in the biotype ratios has been observed: the B biotype has come to predominate over the Q biotype ranging up to 90% or more in most fields. At the same time, resistance to the IGR pyriproxyfen was reduced considerably. CONCLUSION The possible reasons for the change in the dynamics of B. tabaci biotypes, and its implications for resistance management, are discussed. Strong B. tabaci resistance to pyriproxyfen in Israel has been associated with the Q rather than with the B biotype. The B biotype is more competitive than the Q biotype under untreated conditions. Reduction in the acreage of cotton fields during recent years, along with a decrease in insecticide use, especially pyriproxyfen, has resulted in the expansion of the B biotype.

Toxicity of spiromesifen to the developmental stages of Bemisia tabaci biotype B

BACKGROUND Spiromesifen is a novel insecticidal/acaricidal compound derived from spirocyclic tetronic acids that acts effectively against whiteflies and mites via inhibition of acetyl-CoA-carboxylase, a lipid metabolism enzyme. The effects of spiromesifen on the developmental stages of the whitefly Bemisia tabaci (Gennadius) were studied under laboratory conditions to generate baseline action thresholds for field evaluations of the compound. RESULTS Adult B. tabaci mortality rate after spiromesifen treatment (5 mg L(-1)) was 40%. Treatment with 0.5 mg L(-1) reduced fecundity per female by more than 80%, and fertility was almost nil. LC(50) for eggs was 2.6 mg L(-1), and for first instar 0.5 mg L(-1). Scanning electron microscopy revealed that eggs laid by treated adult females had an abnormally perforated chorion, and females were unable to complete oviposition. Light and fluorescent microscopy showed significantly smaller eggs following treatment, and smaller, abnormally formed and improperly localized bacteriomes in eggs and nymphs. The number of ovarioles counted in females treated with 5 mg L(-1) was significantly reduced. Spiromesifen showed no cross-resistance with other commonly used insecticides from different chemical groups, and resistance monitoring in Israel showed no development of field resistance to this insecticide after 1 year of use. CONCLUSION The strong effect on juvenile stages of B. tabaci with a unique mode of action and the absence of cross-resistance with major commonly used insecticides from different chemical groups suggest the use of spiromesifen in pest and resistance management programmes.

Cypermethrin synergism by pyrethroid esterase inhibitors in adults of the whitefly Bemisia tabaci

Abstract Pyrethroid esterases are a major factor in the tolerance of adults of the whitefly Bemesia tabaci to cypermethrin and related pyrethroids. This conclusion is based on the substrate specificity of these esterases and their inhibition by organophosphorus compounds acting as synergists. Whitefly esterases hydrolyze trans -permethrin faster than its cis -isomer or its α-cyano analogs trans - and cis -cypermethrin and deltamethrin. With trans -permethrin as the substrate, these pyrethroid esterases are sensitive to in vitro inhibition by monocrotophos and methamidophos (the active metabolite of acephate) with 50% inhibition at 9 × 10 −7 and 10 −5 M , respectively. The potency of cypermethrin under glasshouse conditions is synergized 5- to 50-fold by monocrotophos, acephate or methidathion and it is also greatly increased by profenofos, with synergist:pyrethroid ratios ranging from 1:8 to 8:1. Cypermethrin toxicity under field conditions in cotton is strongly synergized and the effective period for whitefly control is prolonged by adding an equal weight of monocrotophos or acephate or 8 parts of methidation to 1 part pyrethroid. Mouse liver pyrethroid esterases hydrolyzing cis -cypermethrin are inhibited by low intraperitoneal doses of profenofos and acephate but not monocrotophos and methidathion. The high magnitude of cypermethrin synergism in whiteflies is not repeated in mice, perhaps due to differences in the toxicological importance and inhibitor specificities of esterases involved in detoxification.

Insecticides with novel modes of action: Mechanism, selectivity and cross-resistance

Efforts have been made during the past two decades to develop insecticides with selective properties that act specifically on biochemical sites present in particular insect groups, but whose properties differ from other insecticides. This approach has led to the discovery of compounds that affect the hormonal regulation of molting and developmental processes in insects; for example, ecdysone agonists, juvenile hormone mimics and chitin synthesis inhibitors. In addition, compounds that selectively interact with the insect nicotinic acetylcholine receptor, such as imidacloprid, acetamiprid and thiamethoxam, have been introduced for the control of aphids, whiteflies and other insect species. Natural products acting selectively on insect pests, such as avermectins, spinosad and azadirachtin, have been introduced for controlling selected groups of insect pests. Compounds acting on the nervous site that controls the sucking pump of aphids and whiteflies, such as pymetrozine, or respiration, such as diafenthiuron, have been introduced for controlling sucking pests. All the above compounds are important components in pest and resistance management programs.

Toxicity and growth-suppression exerted by diafenthiuron in the sweetpotato whitefly,Bemisia tabaci

Diafenthiuron (CGA 106 ’630), a thiourea, was sprayed prior to a 48-h infestation by adult females of the sweetpotato whiteflyBemisia tabaci Gennadius, on cotton seedlings under greenhouse conditions; it subsequently suppressed strongly progeny formation of the whitefly, resulting in approximately 50% progeny formation relative to control at 5 mg a.i./l. When the different development stages were separately sprayed directly, the larval stage was the most susceptible, resulting in 50% and 90% mortality of 2nd instars at concentrations of 6.5 and 49.2 mg a.i./l, whereas the LC50 values of adults and pupae were 23 and 45 mg a.i./l, respectively. A mild (30–35%) reduction of egg hatch was obtained at a range of 5–125 mg a.i./l. Thus the potency of diafenthiuron against various stages was in the order larvae > adults > pupae > eggs. Diafenthiuron exhibited a low vapor phase toxicity and had no translaminar effect when tested on first instars ofB. tabaci. The high potency of diafenthiuron against whiteflies described herein, against aphids and mites, as stated in the literature, and against some lepidopterous pests, render this compound an important insect control agent for pests of cotton and other crops.