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 J Bottery; Michael J Bromley

doi:10.1038/s41564-023-01542-4

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 J Bottery, Michael J Bromley

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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.

Original language	English
Pages (from-to)	29-34
Number of pages	6
Journal	Nature Microbiology
Volume	9
Issue number	1
Early online date	27 Dec 2023
DOIs	https://doi.org/10.1038/s41564-023-01542-4
Publication status	Published - 1 Jan 2024

Keywords

Aspergillus fumigatus/genetics
Fungicides, Industrial/pharmacology
Agrochemicals
Pyrroles/pharmacology
Antifungal Agents/pharmacology

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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.",

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AU - Oliver, Jason D

AU - Bottery, Michael J

AU - Bromley, Michael J

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Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim

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