title: Fluensulfone is a nematicide with a mode of action distinct from anticholinesterases and macrocyclic lactones.
abstract: Plant parasitic nematodes infest crops and present a threat to food security worldwide. Currently available chemical controls e.g. methyl bromide, organophosphates and carbamates have an unacceptable level of toxicity to non-target organisms and are being withdrawn from use. Fluensulfone is a new nematicide of the fluoroalkenyl thioether group that has significantly reduced environmental impact with low toxicity to non-target insects and mammals. Here, we show that the model genetic organism Caenorhabditis elegans is susceptible to the irreversible nematicidal effects of fluensulfone. Whilst the dose required is higher than that which has nematicidal activity against Meloidogyne spp. the profile of effects on motility, egg-hatching and survival is similar to that reported for plant parasitic nematodes. C. elegans thus provides a tractable experimental paradigm to analyse the effects of fluensulfone on nematode behaviour. We find that fluensulfone has pleiotropic actions and inhibits development, egg-laying, egg-hatching, feeding and locomotion. In the case of feeding and locomotion, an early excitation precedes the gross inhibition. The profile of these effects is notably distinct from other classes of anthelmintic and nematicide: the inhibition of motility caused by fluensulfone is not accompanied by the hypercontraction which is characteristic of organophosphates and carbamates and C. elegans mutants that are resistant to the carbamate aldicarb and the macrocyclic lactone ivermectin retain susceptibility to fluensulfone. These data indicate fluensulfone's mode of action is distinct from currently available nematicides and it therefore presents a promising new chemical entity for crop protection.
authors.affiliation: Centre for Biological Sciences, University of Southampton, Building 85, University Road, Southampton SO17 1BJ, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Kearn
authors.affiliation: Centre for Biological Sciences, University of Southampton, Building 85, University Road, Southampton SO17 1BJ, United Kingdom.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Ludlow
authors.affiliation: Centre for Biological Sciences, University of Southampton, Building 85, University Road, Southampton SO17 1BJ, United Kingdom.
authors.forename: James
authors.initials: J
authors.lastname: Dillon
authors.affiliation: Centre for Biological Sciences, University of Southampton, Building 85, University Road, Southampton SO17 1BJ, United Kingdom.
authors.forename: Vincent
authors.initials: V
authors.lastname: O'Connor
authors.affiliation: Centre for Biological Sciences, University of Southampton, Building 85, University Road, Southampton SO17 1BJ, United Kingdom. Electronic address: lmhd@soton.ac.uk.
authors.forename: Lindy
authors.initials: L
authors.lastname: Holden-Dye
mesh_terms: D000448:Aldicarb / Q000633:toxicity; D000818:Animals; D000969:Antinematodal Agents / Q000633:toxicity*; D001522:Behavior, Animal / Q000187:drug effects; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000502:physiology; D002800:Cholinesterase Inhibitors / Q000633:toxicity; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity; D007559:Ivermectin / Q000633:toxicity; D009043:Motor Activity / Q000187:drug effects; D010614:Pharynx / Q000187:drug effects / Q000502:physiology; D012098:Reproduction / Q000187:drug effects; D013450:Sulfones / Q000633:toxicity*; D013844:Thiazoles / Q000633:toxicity*
chemical_list: D000969:Antinematodal Agents; D002800:Cholinesterase Inhibitors; D007306:Insecticides; D013450:Sulfones; D013844:Thiazoles; D007559:Ivermectin; D000448:Aldicarb; C571996:fluensulfone
keywords: Behaviour; Caenorhabditis elegans; Electrophysiology; Nematode; Parasitic; Plant