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Selective Control of Parasitic Nematodes Using Bioactivated Nematicides

Burns, A. R.; Ross, R. J.; Kitner, M.; Volpatti, J.; Vaidya, A. S.; Puumala, E.; Palmeira, B. M.; Redman, E. M.; Snider, J.; Marwah, S.; Chung, S. W.; MacDonald, M. H.; Tiefenbach, J.; Hu, C.; Xiao, Q.; Finney, C. A. M.; Krause, H.; MacParland, S.; Stagljar, I.; Gilleard, J. S.; Cowen, L.; Meyer, S. L. F.; Cutler, S. R.; Dowling, J. J.; Lautens, M.; Zasada, I.; Roy, P.

2022-03-14 pharmacology and toxicology
10.1101/2022.03.11.483960 bioRxiv
Show abstract

Parasitic nematodes are a major threat to global food security, particularly as the world amasses 10 billion people amidst limited arable land. Most traditional nematicides have been banned due to poor nematode-selectivity, leaving farmers with inadequate controls. Here, we use the model nematode Caenorhabditis elegans to identify a family of selective imidazothiazole nematicides, called selectivins, that undergo cytochrome p450-dependent bioactivation exclusively in nematodes. At low parts-per-million concentrations, selectivins perform comparably well with commercial nematicides to control root infection by Meloidogyne incognita - the worlds most destructive plant-parasitic nematode. Tests against a wide range of phylogenetically diverse non-target systems demonstrate that selectivins are more nematode-selective than nearly all marketed nematicides. Thus, selectivins are first-in-class bioactivated nematode controls that provide efficacy as well as much-needed nematode selectivity.

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