Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim
Norman van Rhijn, Isabelle S. R. Storer, Mike Birch, Jason D. Oliver, Michael Bottery, Michael Bromley
Abstract
Widespread use of azole antifungals in agriculture has been linked to resistance in the pathogenic fungus Aspergillus fumigatus. We show that exposure of A. fumigatus to the agrochemical fungicide, ipflufenoquin, in vitro can select for strains that are resistant to olorofim, a first-in-class clinical antifungal with the same mechanism of action. Resistance is caused by non-synonymous mutations within the target of ipflufenoquin/olorofim activity, dihydroorotate dehydrogenase (DHODH), and these variants have no overt growth defects.
Topics & Concepts
Aspergillus fumigatusFungicideDihydroorotate dehydrogenaseMicrobiologyBiologyAspergillusAzoleAgrochemicalFungusIn vitroCross-resistanceAntifungalTriazoleChemistryEnzymeGeneticsBiochemistryBotanyAgricultureEcologyOrganic chemistryAntifungal resistance and susceptibilityFungal Plant Pathogen ControlSynthesis and Biological Evaluation