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Cited by 86Antifungal resistance and susceptibilityFungal Plant Pathogen ControlFungal and yeast genetics research

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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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van Rhijn, Norman, Storer, Isabelle S. R., Birch, Mike, Oliver, Jason D., Bottery, Michael J., Bromley, Michael J.·2023·Nature Microbiology
DOI 10.1038/s41564-023-01542-4PMC PMC10769868

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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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Research works printed but not linked: 27

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Metadata

Authors
van Rhijn, N., Storer, I. S. R., Birch, M., Oliver, J. D., Bottery, M. J., & Bromley, M. J.
Affiliations
  • University of Manchester (GB)
  • F2G (United Kingdom) (GB)
Corresponding author
Bromley, Michael J.
ORCID
Venue
Nature Microbiology
Publisher
Springer Science and Business Media LLC
Published
2023-12-27
Volume
9
Issue
1
Pages
29-34
ISSN
2058-5276 (ISSN-L)
DOI
10.1038/s41564-023-01542-4
PMC
PMC10769868
OpenAlex
W4390273837
Cited by
86
References
2
Citations by year
2026: 31 · 2025: 35 · 2024: 19 · 2023: 1
FWCI
17.80
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature Microbiology (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, cc-by)
  • UEA Digital Repository (University of East Anglia) (acceptedVersion)
Funders
  • Wellcome Trust (219551/Z/19/Z, 226408/Z/22/Z, 221653/Z/20/Z)
  • RCUK | Medical Research Council (DTP)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Antifungal resistance and susceptibility
  • Life Sciences › Agricultural and Biological Sciences › Plant Science › Fungal Plant Pathogen Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
Aspergillus fumigatus, olorofim, fungicide resistance, azole resistance, dihydroorotate dehydrogenase, non-synonymous mutations, fungicide selection
MeSH terms
Acetamides, Antifungal Agents, Aspergillus fumigatus, Fungicides, Industrial, Piperazines, Pyrimidines, Pyrroles, Agrochemicals

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