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Jun 05, 2024;

mutations provide an alternative mechanism for 5-FOA resistance in .

Joseph O Armstrong, Pengyao Jiang, Skyler Tsai, Megan My-Ngan Phan, Kelley Harris, Maitreya J Dunham
Author Information
  1. Joseph O Armstrong: Department of Genome Sciences, University of Washington. ORCID
  2. Pengyao Jiang: Department of Genome Sciences, University of Washington. ORCID
  3. Skyler Tsai: Department of Genome Sciences, University of Washington.
  4. Megan My-Ngan Phan: Department of Genome Sciences, University of Washington.
  5. Kelley Harris: Department of Genome Sciences, University of Washington. ORCID
  6. Maitreya J Dunham: Department of Genome Sciences, University of Washington. ORCID
PMID: 38895202 DOI: 10.1101/2024.06.03.597250

Abstract

is frequently used in the yeast community as the mutation target for 5-fluoroorotic acid (5-FOA) resistance. We identified a novel class of mutants that can grow in the presence of 5-FOA. Unlike mutants, mutants remain prototrophic and grow in the absence of uracil. In addition to 5-FOA resistance, we found that mutations to also confer resistance to 5-fluorocytosine (5-FC) and 5-fluorouracil (5-FU). In total, we identified 50 unique missense mutations across 32 residues of . We found that 28 out of the 32 affected residues are located in regions conserved between and three clinically relevant pathogenic fungi. These findings suggest that mutations to present a second target for mutation screens utilizing 5-FOA as a selection marker as well as a potential mode of resistance to the antifungal therapeutic 5-FC.

References

  1. Mol Gen Genet. 1988 Nov;214(3):396-404 [PMID: 3063945]
  2. Nucleic Acids Res. 2023 Jan 6;51(D1):D523-D531 [PMID: 36408920]
  3. Mol Biol Evol. 2013 Apr;30(4):772-80 [PMID: 23329690]
  4. Nat Ecol Evol. 2022 Oct;6(10):1501-1515 [PMID: 36050399]
  5. Front Microbiol. 2021 Sep 10;12:712631 [PMID: 34566920]
  6. Genome Biol Evol. 2011;3:799-811 [PMID: 21666225]
  7. Nat Commun. 2021 Jan 20;12(1):482 [PMID: 33473124]
  8. Appl Microbiol Biotechnol. 2009 Jun;83(4):783-9 [PMID: 19455322]
  9. Nat Methods. 2019 Jun;16(6):453-454 [PMID: 31133757]
  10. Mol Gen Genet. 1986 Oct;205(1):74-81 [PMID: 3025561]
  11. Nat Struct Mol Biol. 2021 Dec;28(12):1020-1028 [PMID: 34887558]
  12. J Fungi (Basel). 2018 Mar 20;4(1): [PMID: 30152809]
  13. Genetics. 2008 Jan;178(1):67-82 [PMID: 18202359]
  14. G3 (Bethesda). 2022 Nov 4;12(11): [PMID: 36173330]
  15. G3 (Bethesda). 2020 Dec 3;10(12):4335-4345 [PMID: 33082270]
  16. Elife. 2021 Sep 15;10: [PMID: 34523420]
  17. BMC Bioinformatics. 2024 Jul 9;25(1):232 [PMID: 38982382]
  18. Evol Lett. 2024 Jul 29;8(6):851-865 [PMID: 39677573]
  19. Mol Gen Genet. 1984;197(2):345-6 [PMID: 6394957]
  20. Nat Commun. 2021 Jun 8;12(1):3418 [PMID: 34103502]
  21. Bio Protoc. 2022 Jun 05;12(11): [PMID: 35799910]
  22. Nature. 2018 Apr;556(7701):339-344 [PMID: 29643504]
  23. Curr Opin Genet Dev. 2021 Dec;71:78-85 [PMID: 34311384]
  24. J Antimicrob Chemother. 2000 Aug;46(2):171-9 [PMID: 10933638]
  25. Nat Rev Cancer. 2003 May;3(5):330-8 [PMID: 12724731]
  26. Proc Natl Acad Sci U S A. 2018 Jul 24;115(30):E7109-E7118 [PMID: 29987035]
  27. PLoS Genet. 2023 Oct 19;19(10):e1011002 [PMID: 37856537]

Grants

  1. R35 GM133428/NIGMS NIH HHS
Journal Article Preprint
Article has an altmetric score of 15

Word Cloud

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