Journal Article
Proceedings of the National Academy of Sciences, vol. 110, iss. 49, pp. 19766-19771, 2013
Authors
Hanafy M. Ismail, Paul M. O’Neill, David W. Hong, Robert D. Finn, Colin J. Henderson, Aaron T. Wright, Benjamin F. Cravatt, Janet Hemingway, Mark J. I. Paine
Abstract
Significance
Pyrethroids are highly potent insecticides used worldwide in ∼3,500 registered products to control diseases spread by arthropods. Although they are critical for controlling a diverse spectrum of diseases, such intense exposure affects health and drives the rapid evolution of insecticide resistance. Here we have developed a suite of pyrethroid mimetic activity-based probes (PyABPs) to selectively label and identify P450s associated with pyrethroid metabolism in highly divergent organisms. Using a rat liver model, we demonstrate that PyABPs detect pyrethroid metabolizing P450s and a network of drug-metabolizing enzymes that is termed the “pyrethrome.” This discovery has broad scientific interest and provides a unique perspective on insecticide interactions, improving understanding of insecticide metabolism and aiding the development of tools for disease control.
