{
  "abstract": "Successful treatment of primary Clostridioides difficile infection (CDI) while preventing its recurrence remains a major clinical challenge, with recurrent CDI (R-CDI) affecting 20-30% of treated patients. Persistence of C. difficile spores within the intestinal mucosa is thought to drive R-CDI following antibiotic treatment. Here, we show that intracellular C. difficile spores remain protected from taurocholate-triggered germination, and that nystatin, an FDA-approved antifungal that blocks spore entry into host cells, reduces this protected intracellular population and redirects spores toward an extracellular, germinating population accessible to antibiotics. In a murine model of R-CDI, oral co-administration of taurocholate with nystatin and antibiotics during primary CDI reduced R-CDI incidence from 100% to 44%. When administered during an active R-CDI episode, the same formulation reduced a second R-CDI from 100% to 62%. To improve bioavailability, we encapsulated nystatin and vancomycin in chitosan nanoparticles. Oral administration of nanoparticle-encapsulated vancomycin, alone or combined with nanoparticle-encapsulated nystatin, reduced R-CDI colonization to 33% and 44%, respectively, compared with 100% in mice receiving free vancomycin. Together, these findings support a therapeutic strategy that repurposes nystatin and taurocholate, in combination with antibiotics and nanoparticle-based delivery, to target intracellular spore persistence and reduce the incidence of C. difficile recurrence..",
  "abstract_shown": true,
  "affiliations": [
    "Texas A and M University"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 14,
  "authors": [
    {
      "name": "P. Castro-Cordova"
    },
    {
      "name": "M. Mendoza-Leon"
    },
    {
      "name": "S. Alamos-Musre"
    },
    {
      "name": "J. Munoz-Miralles"
    },
    {
      "name": "F. Diaz-Yanez"
    },
    {
      "name": "F. Marchant-Llancalahuen"
    },
    {
      "name": "D. Cea"
    },
    {
      "name": "R. Hernandez-Armengol"
    },
    {
      "name": "J. Valeria"
    },
    {
      "name": "K. Mondaca"
    },
    {
      "name": "C. Otero"
    },
    {
      "name": "F. Gil"
    },
    {
      "name": "M. Pizarro-Guajardo"
    },
    {
      "affs": [
        0
      ],
      "name": "D. Paredes-Sabja"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5r7yqgf1pvg8v.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.09.25.754266",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754266v1.full",
  "id": "5r7yqgf1pvg8v",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754266v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "pharmacology and toxicology"
    ],
    [
      "openalex",
      "2725|Clostridium difficile and Clostridium perfringens research"
    ]
  ],
  "openalex": "W7215128348",
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754266v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-09-25",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5r7yqgf1pvg8v.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:25:38Z",
      "native_id": "10.64898/2026.09.25.754266",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.09.25.754266v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "biorxiv:pharmacology and toxicology",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Repurposing nystatin and taurocholate to target intracellular spore persistence during antibiotic treatment to prevent recurrent Clostridioides difficile infection.",
  "title_text": "Repurposing nystatin and taurocholate to target intracellular spore persistence during antibiotic treatment to prevent recurrent Clostridioides difficile infection.",
  "type": "preprint",
  "updated_at": "2026-10-30T12:25:38Z",
  "url": "https://research.draconitic.com/paper/5r7yqgf1pvg8v",
  "venue": "bioRxiv",
  "versions": []
}