Evidence map›Paper›PMID 40569759›Full record

ArticleThe Journal of infectious diseases2025

A Candidozyma (Candida) auris-Optimized Episomal Plasmid-Induced Cas9-Editing System Reveals the Direct Impact of the S639F-Encoding FKS1 Mutation.

Laura A Doorley, Vanessa Meza-Perez, Sarah J Jones, Jeffrey M Rybak

Abstract read
In one paragraph

Article in The Journal of infectious diseases, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

8 citing papers in PubMed.

  1. Review
  2. Deciphering the multidrug resistance paradigm inAntimicrobial agents and chemotherapy · 2026
    Review
  3. ER stress selects forFrontiers in microbiology · 2026
    Article
  4. Article
  5. Acquired amphotericin B resistance attributed to a mutatedAntimicrobial agents and chemotherapy · 2025
    Article
  6. Article
  7. Article
  8. Acquired Amphotericin B Resistance Attributed to a MutatedbioRxiv : the preprint server for biology · 2025
    Article
4 · The record

Corrections and comments

  • Update of
    A2025
5 · Who and what money

Authors and funding

4 authors.

Laura A DoorleyDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-1695-9561
Vanessa Meza-PerezDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-6828-5618
Sarah J JonesDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0009-0003-4739-5257
Jeffrey M RybakDepartment of Pharmacy and Pharmaceutical Sciences, St Jude Children's Research Hospital, Memphis, Tennessee, USA.ORCID 0000-0002-9317-0935

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
American Lebanese Syrian Associated CharitiesHartwell Center for Bioinformatics and BiotechnologyNCI NIH HHS P30 CA021765Society of Infectious Diseases Pharmacists Young Investigator ResearchSt Jude Center for Advanced Genome EngineeringSt Jude Children's Research Hospital Children's Infection Defense Center
6 · The paper itself

Abstract

backgroundMutations in the Candidozyma (Candida) auris β-glucan synthase gene (FKS1) altering S639 are frequently associated with clinical echinocandin resistance. We have developed a novel C auris-optimized episomal plasmid-induced Cas9 (EPIC) gene-editing system capable of recyclable precision editing and demonstrate the contribution of FKS1S639F mutation to echinocandin resistance.

methodsThe EPIC gene-editing system was generated for optimized use in C auris, and ADE2 modification was evaluated in 5 C auris clades. Mutations leading to Fks1S639F and Fks1WT were placed into echinocandin-susceptible and echinocandin-resistant isolates from clades III and I, respectively. Echinocandin susceptibility was determined by Clinical and Laboratory Standards Institute methods. Cell wall abundance of chitin and β-glucan was assessed by staining with calcofluor white and aniline blue.

resultsThe EPIC system was capable of targeted ADE2 editing in all tested C auris isolates and precise editing confirmed by sequencing. A single-nucleotide polymorphism (SNP) in FKS1 resulting in either the S639F substitution or a synonymous mutation was introduced in an echinocandin-susceptible clade III isolate. Precision FKS1 editing by the EPIC system was confirmed by whole genome sequencing. Introduction of the Fks1S639F allele increased echinocandin resistance, while correction of the Fks1S639F to the Fks1WT sequence in an echinocandin-resistant clade I isolate restored echinocandin sensitivity. Evaluation of cell wall composition showed strains harboring Fks1S639F to contain significantly elevated β-glucan and chitin content.

conclusionsThese data demonstrate the potential of our EPIC system in its ability to introduce SNPs in multiple C auris clade backgrounds while revealing the direct impact of the S639F-encoding FKS1 mutation on echinocandin resistance.

Indexed as

Candida aurisFungal ProteinsGene EditingGlucosyltransferasesPlasmidsAntifungal Agentsbeta-GlucansCRISPR-Cas SystemsDrug Resistance, FungalEchinocandinsHumansMicrobial Sensitivity TestsMutationAntifungal Agentsbeta-GlucansEchinocandinsFungal Proteinsglucan synthaseGlucosyltransferasesCandida aurisCRISPRFKS1gene editingresistance

Identifiers

PMID40569759
PMCPMC12455316

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.