{
  "abstract": "Fosfomycin is increasingly used to treat multidrug-resistant Gram-negative infections, yet resistance surveillance largely relies on homology-based detection of known fos genes. Here, we identify Gfa, a previously unrecognized integron-borne fosfomycin resistance determinant uncovered through functional screening of 129 integron gene cassettes. Gfa confers high-level fosfomycin resistance across Enterobacterales and Pseudomonas aeruginosa and is resistant to phosphonoformate inhibition. Structural modelling and mutagenesis reveal a conserved cysteine-rich, zinc-organized architecture essential for activity and distinct from canonical Fos enzymes. Crude-extract assays confirm glutathione-dependent fosfomycin inactivation under metal-chelating conditions. Distant Gfa homologs also conferred resistance, although activity was restricted to a subset of proteins tested. Together, these findings establish Gfa as a previously unrecognized fosfomycin resistance family and highlight the limitations of homology-based mining for discovering novel resistance determinants and predicting which family members are functional.",
  "abstract_shown": true,
  "affiliations": [
    "IMIBIC"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "N. Kieffer"
    },
    {
      "name": "A. Prieto"
    },
    {
      "name": "L. Ortiz-Miravalles"
    },
    {
      "name": "A. Hipolito"
    },
    {
      "name": "E. Vergara"
    },
    {
      "name": "J. Borrero del Pino"
    },
    {
      "name": "A. Carvalho"
    },
    {
      "name": "J.-A. Escudero"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/bgwsqdf0gpgt3.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.07.757220",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757220v1.full",
  "id": "bgwsqdf0gpgt3",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757220v1",
  "language": null,
  "licence": "CC-BY-NC",
  "licence_label": "CC BY-NC",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "microbiology"
    ],
    [
      "openalex",
      "1313|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7220956424",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757220v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-07",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/bgwsqdf0gpgt3.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:26:40Z",
      "native_id": "10.64898/2026.10.07.757220",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.10.07.757220v2"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:microbiology",
      "subfield": "microbiology"
    }
  ],
  "title": "Gfa, a new integron-borne fosfomycin resistance family",
  "title_text": "Gfa, a new integron-borne fosfomycin resistance family",
  "type": "preprint",
  "updated_at": "2026-10-30T12:26:58Z",
  "url": "https://research.draconitic.com/paper/bgwsqdf0gpgt3",
  "venue": "bioRxiv",
  "versions": []
}