Selective Control of Parasitic Nematodes Using Bioactivated Nematicides

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 world’s 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.

The marksman: Bioactivated nematicides selectively kill plant‐parasitic nematodes

“…Recently, Burns et al (2023), when screening uncharacterized compounds that disrupted the growth of the free‐living nematode Caenorhabditis elegans , discovered a new class of nematicides that contain imidazothiazole, and found that they were highly selective in killing only nematodes (Figure 1A). Experiments using various nematode species and a wide range of non‐nematode species and cell types indicated that the newly discovered nematicides, called selectivins, exhibit even higher selectivity for nematodes than most commercially available formulations tested.…”

“…Recently, Burns et al (2023), when screening uncharacterized compounds that disrupted the growth of the free-living nematode Caenorhabditis elegans, discovered a…”

“…There have been hardly any safer alternatives developed to replace them, which leaves the farmers with limited options to control nematodes, endangering global food security. Therefore, there is great demand to develop nematode-selective nematicides.Recently, Burns et al (2023), when screening uncharacterized compounds that disrupted the growth of the free-living nematode Caenorhabditis elegans, discovered a…”

Diverse Plant-Parasitic Nematodes are Selectively Killed by Oxadiazole Thioether Pro-Nematicides

“…Our group recently discovered a novel class of imidazothiazole compounds called the Selectivins that selectivity kill nematodes via cytochrome P450-mediated bioactivation ( 8 ). Xenobiotic-metabolizing cytochrome P450 enzymes (P450s) typically detoxify their substrates, catalyzing monooxygenation reactions that enhance substrate hydrophilicity and promote metabolite excretion via drug efflux pumps ( 9 ).…”

“…However, some substrate-P450 pairs transform a relatively inert compound into a metabolite that exhibits novel or heightened biological activity ( 10–12 ). This bioactivation can be phylum or species-selective due to the vast phylogenetic diversity of P450s ( 8 , 13 ). Indeed, we have shown that the Selectivins are selectively bioactivated by specific nematode P450s into reactive electrophilic products that kill nematodes but not non-target species from diverse phyla ( 8 ).…”