The novel agrochemical fungicide ipflufenoquin drives cross-resistance to olorofim in the human pathogen Aspergillus fumigatus.

Abstract Widespread use of azole antifungals in agriculture has driven a pandemic of resistance in the pathogenic fungus Aspergillus fumigatus . A novel clinical antifungal, olorofim, promises to alleviate this problem but as it nears approval, a new agrochemical fungicide, ipflufenoquin with the same mechanism of action, has been approved by the US EPA. We show that exposure of A. fumigatus to ipflufenoquin can select for strains that are resistant to olorofim, potentially undermining decades of effort in clinical antifungal drug development.