Investigating the mode of action of sulfoxaflor: a fourth-generation neonicotinoid.

BACKGROUND: The precise mode of action of sulfoxaflor, a new nicotinic acetylcholine receptor-modulating insecticide, is unclear. A detailed understanding of the mode of action, especially in relation to the neonicotinoids, is essential for recommending effective pest management practices. RESULTS: Radiolabel binding experiments using a tritiated analogue of sulfoxaflor ([(3) H]-methyl-SFX) performed on membranes from Myzus persicae demonstrate that sulfoxaflor interacts specifically with the high-affinity imidacloprid binding site present in a subpopulation of the total nAChR pool. In competition studies, imidacloprid-like neonicotinoids displace [(3) H]-methyl-SFX at pM concentrations. The effects of sulfoxaflor on the exposed aphid nervous system in situ are analogous to those of imidacloprid and nitenpyram, and finally the high-affinity sulfoxaflor binding site is absent in a Myzus persicae strain (clone FRC) possessing a single amino acid point mutation (R81T) in the ß-nAChR, a region critical for neonicotinoid interaction. CONCLUSION: The nicotinic acetylcholine receptor pharmacological profile of sulfoxaflor in aphids is consistent with that of imidacloprid. Additionally, the insecticidal activity of sulfoxaflor and the current commercialised neonicotinoids is affected by the point mutation in FRC Myzus persicae. Therefore, it is suggested that sulfoxalfor be considered a neonicotinoid, and that this be taken into account when recommending insecticide rotation partnering for effective resistance management programmes.

Identifying the presence of neonicotinoidresistant peach-potato aphid (Myzus persicae) in the peach-growing regions of southern France and northern Spain.

BACKGROUND: The neonicotinoid class of insecticides is a key component of pest management strategies used by stone fruit producers in Europe. Neonicotinoids are currently one of the most important tools for control of the peach-potato aphid (Myzus persicae). Overreliance on neonicotinoids has led to the development of resistance through a combination of metabolic and target-site resistance mechanisms in individual aphids. A resistance monitoring project was conducted by Syngenta in 2010 to determine the resistance status of M. persicae populations collected from France and Spain, and to determine the frequency of the target-site mutation in those populations. RESULTS: Resistance monitoring suggests that resistance to neonicotinoids is relatively widespread in populations of M. persicae collected from peach orchards in the Languedoc-Roussillon, Provence-Alpes-Cote d'Azur and Rhone-Alpes regions of France, and resistance can be associated with the frequency of the target-site mutation (R81T). The R81T mutation in its heterozygous form is also present in Spanish populations and is associated with neonicotinoid resistance. CONCLUSION: The widespread nature of neonicotinoid resistance in southern France and the potential for resistance development in northern Spain highlight the need for a coordinated management strategy employing insecticides with different modes of action to reduce the selection pressure with neonicotinoids.

Mutation of a nicotinic acetylcholine receptor ß subunit is associated with resistance to neonicotinoid insecticides in the aphid Myzus persicae.

BACKGROUND: Myzus persicae is a globally important aphid pest with a history of developing resistance to insecticides. Unusually, neonicotinoids have remained highly effective as control agents despite nearly two decades of steadily increasing use. In this study, a clone of M. persicae collected from southern France was found, for the first time, to exhibit sufficiently strong resistance to result in loss of the field effectiveness of neonicotinoids. RESULTS: Bioassays, metabolism and gene expression studies implied the presence of two resistance mechanisms in the resistant clone, one based on enhanced detoxification by cytochrome P450 monooxygenases, and another unaffected by a synergist that inhibits detoxifying enzymes. Binding of radiolabeled imidacloprid (a neonicotinoid) to whole body membrane preparations showed that the high affinity [3H]-imidacloprid binding site present in susceptible M. persicae is lost in the resistant clone and the remaining lower affinity site is altered compared to susceptible clones. This confers a significant overall reduction in binding affinity to the neonicotinoid target: the nicotinic acetylcholine receptor (nAChR). Comparison of the nucleotide sequence of six nAChR subunit (Mpα1-5 and Mpß1) genes from resistant and susceptible aphid clones revealed a single point mutation in the loop D region of the nAChR ß1 subunit of the resistant clone, causing an arginine to threonine substitution (R81T). CONCLUSION: Previous studies have shown that the amino acid at this position within loop D is a key determinant of neonicotinoid binding to nAChRs and this amino acid change confers a vertebrate-like character to the insect nAChR receptor and results in reduced sensitivity to neonicotinoids. The discovery of the mutation at this position and its association with the reduced affinity of the nAChR for imidacloprid is the first example of field-evolved target-site resistance to neonicotinoid insecticides and also provides further validation of exisiting models of neonicotinoid binding and selectivity for insect nAChRs.