Discovery and biological characterization of a novel mesoionic insecticide fenmezoditiaz.

BACKGROUND: Many piercing-sucking insects have developed resistance or cross-resistance to many insecticides targeting insect neural nicotinic acetylcholine receptor (nAChR). Here we are aiming to present the discovery of a novel mesoionic insecticide, fenmezoditiaz, by BASF through structure-based drug design (SBDD) approaches. It has recently been added to the Insecticide Resistance Action Committee mode of classification (IRAC 4E). It is being developed for plant protection against piercing-sucking pests, especially rice hopper complex. RESULTS: The soluble acetylcholine binding protein (AChBP) from the sea slug Aplysia californica was modified using site-directed mutagenesis and based on putative aphid nAChR subunit sequences to create soluble insect-like AChBPs. Among them, insect-like ß1 AChBP and native aphid membrane preparation showed the highest correlated biochemical affinity toward structurally diverse ligands. This mutant AChBP was used to understand how insect nAChRs structurally interact with mesoionics, which was then utilized to design novel mesoionics including fenmezoditiaz. It is an excellent systemic insecticide with diverse application methods and has a broad insecticidal spectrum, especially against piercing/sucking insects. It lacks cross-resistance for neonicotinoid resistant plant hoppers. Field-collected brown plant hopper populations from Asian countries showed high susceptibility. CONCLUSIONS: Fenmezoditiaz is a systemic insecticide with a broad spectrum, lack of cross-resistance and it could be an additional tool for integrated pest management and insecticide resistance management, especially for the rice hopper complex. © 2024 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

TRP Channels in Insect Stretch Receptors as Insecticide Targets.

Defining the molecular targets of insecticides is crucial for assessing their selectivity and potential impact on environment and health. Two commercial insecticides are now shown to target a transient receptor potential (TRP) ion channel complex that is unique to insect stretch receptor cells. Pymetrozine and pyrifluquinazon disturbed Drosophila coordination and hearing by acting on chordotonal stretch receptor neurons. This action required the two TRPs Nanchung (Nan) and Inactive (Iav), which co-occur exclusively within these cells. Nan and Iav together sufficed to confer cellular insecticide responses in vivo and in vitro, and the two insecticides were identified as specific agonists of Nan-Iav complexes that, by promoting cellular calcium influx, silence the stretch receptor cells. This establishes TRPs as insecticide targets and defines specific agonists of insect TRPs. It also shows that TRPs can render insecticides cell-type selective and puts forward TRP targets to reduce side effects on non-target species.

QUANTITATIVE GENETIC ANALYSIS OF DIVERGENCE IN MALE SECONDARY SEXUAL TRAITS BETWEEN DROSOPHILA SIMULANS AND DROSOPHILA MAURITIANA.

The sibling species Drosophila simulans and D. mauritiana differ significantly in a number of male secondary sexual traits, providing an ideal system for genetic analysis of interspecific morphological divergence. In the experiment reported here, F1 hybrids from a cross of two inbred lines were backcrossed in both directions and about 200 flies from each backcross were scored for several traits (bristle numbers and cuticle areas), as well as 18 markers distributed throughout the genome. Each trait was analyzed by composite interval mapping to identify quantitative trait loci (QTL) and estimate their effects. For each trait, from one to eight loci were detected, with more divergent traits showing evidence for greater numbers of QTL. Estimates of additive effects varied widely, with a range of 0.4 to 4.1 environmental standard deviation units and an average of 2.2 units. There was substantial evidence for nonadditive effects, since the magnitude of estimates often differed significantly between the two backcrosses. The sign of the estimated effect differed among QTL for bristle traits, but not for cuticle area traits, suggesting that these two types of trait may have undergone different types of selection. Finally, several similarities were found between different traits in the estimated positions of QTL, suggesting that pleiotropy and/or linkage of QTL may have been important in the evolution of these traits.