Burns, Andrew et al. (2021) International Worm Meeting "Selective Control of Parasitic Nematodes with Bioactivated Nematicides"

Volpatti, Jonathan, Palmeira, Bruna, Finney, Constance, Xiao, Qi, Ross, Rachel, Burns, Andrew, Dowling, James, Castelli, Jack, Cowen, Leah, Redman, Elizabeth, Kitner, Megan, Cutler, Sean, Roy, Peter, MacDonald, Margaret, MacParland, Sonya, Puumala, Emily, Snider, Jamie, Zasada, Inga, Meyer, Susan, Lautens, Mark, Vaidya, Aditya, Hu, Chun, Krause, Henry, Marwah, Sagar, Gilleard, John, Chung, Sai, Tiefenbach, Jens, Stagljar, Igor

[International Worm Meeting, 2021]

Global food security is threatened as the world amasses 10 billion people amid limited arable land. While nematode pests are a major barrier to agricultural intensification, most traditional nematicides are now banned because of poor nematode-selectivity, leaving farmers with inadequate controls. Here, we describe a screen carried out in the model nematode Caenorhabditis elegans that enriches for selective nematicides by identifying molecules that are bioactivated by cytochrome P450s, which are phylogenetically diverse. We identify a family of structures, called nemactivins, that are robustly bioactivated to a toxic metabolite selectively in nematodes. At low parts-per-million concentrations, nemactivins perform comparably well with commercial nematicides at controlling infection by the world's most destructive plant-parasitic nematode Meloidogyne incognita. Hence, nemactivins are first-in-class bioactivated nematicides that provide much needed nematode-selectivity.