{
  "abstract": "The emerging fungus Candida auris is a drug resistant global public health threat and WHO critical priority pathogen. Recommended first-line invasive candidiasis treatment is echinocandin monotherapy, but C. auris can develop on-treatment resistance via FKS1/2 gene mutations and additional, previously unexplained mechanisms. To better understand echinocandin failure in C. auris , we sequenced the genomes of echinocandin refractory FKS1/2 wild-type C. auris serial isolates from two critically unwell patients in London, UK. Population analysis profiling revealed echinocandin heteroresistance, and in vitro culture of clinical isolates at supra-MIC concentrations of anidulafungin (8 μg/ml) exhibited morphotypic heterogeneity. Small colony variants (SCVs) and large colony variants (LCVs) showed elevated MICs with polyploidy (to 4n and above) alongside adaptive changes in cell wall β−1,3-glucan content. LCVs contained significantly more mutations in calcineurin-related stress tolerance pathway gene CRZ1 compared to clinical parents and SCVs, associated with further increases in MIC. These findings indicate progressive step-wise accrual of adaptation to echinocandins, including genomic instability, alterations in stress tolerance pathways, and cell wall remodelling, paving the way for resistance emergence.",
  "abstract_shown": true,
  "affiliations": [
    "MRC Center for Medical Mycology at the University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, United Kingdom, EX4 4QD, UK. h.gifford@exeter.ac.uk.",
    "MRC Center for Medical Mycology at the University of Exeter, Geoffrey Pope Building, Stocker Road, Exeter, United Kingdom, EX4 4QD, UK.",
    "Institute of Infection & Immunity, St George's School of Health and Medical Sciences, City St George's University London, United Kingdom, SW17 0RE, UK.",
    "King's College Hospital, Denmark Hill, London, SE5 9RS, UK."
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 13,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hugh Gifford",
      "orcid": "0000-0003-2797-852X"
    },
    {
      "affs": [
        1
      ],
      "name": "Arnab Pradhan"
    },
    {
      "affs": [
        2
      ],
      "name": "Ben Caswall"
    },
    {
      "affs": [
        2
      ],
      "name": "Sarah E Murphy"
    },
    {
      "affs": [
        1
      ],
      "name": "Ian Leaves",
      "orcid": "0000-0002-5612-9087"
    },
    {
      "affs": [
        1
      ],
      "name": "Matt B Edmondson"
    },
    {
      "affs": [
        1
      ],
      "name": "Tanmoy Chakraborty",
      "orcid": "0000-0003-3150-5768"
    },
    {
      "affs": [
        1
      ],
      "name": "Duncan Wilson",
      "orcid": "0000-0001-6617-0123"
    },
    {
      "affs": [
        3
      ],
      "name": "Surabhi K Taori"
    },
    {
      "affs": [
        1
      ],
      "name": "Neil A R Gow",
      "orcid": "0000-0002-2776-5850"
    },
    {
      "affs": [
        1
      ],
      "name": "Rhys A Farrer",
      "orcid": "0000-0001-8456-7458"
    },
    {
      "affs": [
        1
      ],
      "name": "Alistair J P Brown",
      "orcid": "0000-0003-1406-4251"
    },
    {
      "affs": [
        1,
        2
      ],
      "name": "Tihana Bicanic"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5dstmxpng300j.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-76954-x",
  "fulltext_url": "https://europepmc.org/articles/PMC13672790",
  "id": "5dstmxpng300j",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://www.nature.com/articles/s41467-026-76954-x",
  "language": "eng",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2725|Antifungal resistance and susceptibility"
    ]
  ],
  "openalex": "W7222142896",
  "pdf_url": "https://www.nature.com/articles/s41467-026-76954-x.pdf",
  "pmcid": "PMC13672790",
  "pmid": "42881167",
  "published": "2026-10-15",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/5dstmxpng300j.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:38Z",
      "native_id": "10.1038/s41467-026-76954-x",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s41467-026-76954-x"
    },
    {
      "first_seen": "2026-10-30T12:18:46Z",
      "native_id": "MED:42881167",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42881167"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2725|Antifungal resistance and susceptibility",
      "subfield": "infectious-disease"
    }
  ],
  "title": "FKS1/2-variant independent mechanisms underlying the emergence of resistance in echinocandin-refractory Candida auris infections",
  "title_text": "FKS1/2-variant independent mechanisms underlying the emergence of resistance in echinocandin-refractory Candida auris infections",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:18:46Z",
  "url": "https://research.draconitic.com/paper/5dstmxpng300j",
  "venue": "Nature Communications",
  "versions": []
}