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

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van Rhijn, Norman, Storer, Isabelle S. R., Birch, Mike, Oliver, Jason D., Bottery, Michael J. and Bromley, Michael J. (2024) Aspergillus fumigatus strains that evolve resistance to the agrochemical fungicide ipflufenoquin in vitro are also resistant to olorofim. Nature Microbiology, 9. pp. 29-34. ISSN 2058-5276

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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.

Item Type:	Article
Additional Information:	Data availability: Source Data are provided with this paper. Raw sequencing reads are available at SRA: PRJNA961782. Human DHODH PDB file was obtained from 2PRH_1 (https://www.rcsb.org/structure/2prh). Correspondence and requests for materials should be addressed to M. J. Bromley. Funding information: N.v.R. was supported by Wellcome Trust (grant: 226408/Z/22/Z), I.S.R.S. was supported by an MRC DTP Studentship, M. J. Bottery was supported by Wellcome Trust (grant: 221653/Z/20/Z), M. J. Bromley was supported by Wellcome Trust (grant: 219551/Z/19/Z and 208396/Z/17/Z).
Uncontrolled Keywords:	microbiology,immunology,applied microbiology and biotechnology,genetics,microbiology (medical),cell biology ,/dk/atira/pure/subjectarea/asjc/2400/2404
Faculty \ School:	Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Related URLs:	http://www.scopus.com/inward/record.url?...
Depositing User:	LivePure Connector
Date Deposited:	20 Aug 2025 16:30
Last Modified:	27 Aug 2025 08:28
URI:	https://ueaeprints.uea.ac.uk/id/eprint/100187
DOI:	10.1038/s41564-023-01542-4

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