{
  "abstract": "Niemann–Pick type C disease is a fatal lysosomal storage disorder caused by mutations in NPC1 or NPC2 , leading to lipid accumulation and progressive neurodegeneration. Current mammalian models recapitulate major pathological features but are limited by long disease courses and low throughput. Here, we establish the plant-pathogenic fungus Colletotrichum orbiculare as a scalable eukaryotic model of Niemann–Pick type C disease. Introduction of disease-associated mutations into fungal NPC1 or NPC2 homologs abolishes pathogenicity, showing that NPC dysfunction compromises lipid-dependent morphogenesis required for host penetration. Conversely, human NPC1 partially restores fungal infection. Together, these findings support functional conservation of NPC-dependent cellular processes across kingdoms. Miglustat and 2-hydroxypropyl-β-cyclodextrin restore pathogenicity through distinct lipid pathways. These complementary modes of rescue indicate that NPC1 and NPC2 dysfunction converges on lipid-dependent morphogenesis closely linked to actin organization. By connecting lipid metabolism, actin organization, and pharmacological rescue to a measurable infection outcome, this fungal model provides a tractable and scalable platform for mechanistic and therapeutic exploration.",
  "abstract_shown": true,
  "affiliations": [],
  "article_type": null,
  "arxiv": null,
  "author_total": 11,
  "authors": [
    {
      "name": "Hodaka Sano",
      "orcid": "0009-0007-0551-4077"
    },
    {
      "name": "Shun Takezawa"
    },
    {
      "name": "Naoya Saomoto"
    },
    {
      "name": "Ayaka Chiba"
    },
    {
      "name": "Chikako Tanaka"
    },
    {
      "name": "Naoki Kato",
      "orcid": "0000-0003-4410-4090"
    },
    {
      "name": "Takumi Nishiuchi"
    },
    {
      "name": "Hikari Nishisaka"
    },
    {
      "name": "Kazuyuki Kitatani",
      "orcid": "0000-0002-8516-6135"
    },
    {
      "name": "Sayo Kodama"
    },
    {
      "name": "Yasuyuki Kubo",
      "orcid": "0000-0002-8600-9705"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/8cqnhc3d8cay8.bib",
  "cited_by": 0,
  "doi": "10.1038/s42003-026-11198-5",
  "fulltext_url": null,
  "id": "8cqnhc3d8cay8",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://www.nature.com/articles/s42003-026-11198-5",
  "language": null,
  "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",
      "2737|Lysosomal Storage Disorders Research"
    ]
  ],
  "openalex": "W7222818910",
  "pdf_url": "https://www.nature.com/articles/s42003-026-11198-5_reference.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-17",
  "publisher": "Springer Science and Business Media LLC",
  "ris": "https://research.draconitic.com/paper/8cqnhc3d8cay8.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:17:50Z",
      "native_id": "10.1038/s42003-026-11198-5",
      "source": "crossref",
      "url": "https://www.nature.com/articles/s42003-026-11198-5"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2737|Lysosomal Storage Disorders Research",
      "subfield": "physiology"
    }
  ],
  "title": "A Colletotrichum orbiculare-based fungal model recapitulates conserved cellular defects of Niemann–Pick type C disease and enables therapeutic evaluation",
  "title_text": "A Colletotrichum orbiculare-based fungal model recapitulates conserved cellular defects of Niemann–Pick type C disease and enables therapeutic evaluation",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:17:50Z",
  "url": "https://research.draconitic.com/paper/8cqnhc3d8cay8",
  "venue": "Communications Biology",
  "versions": []
}