{
  "abstract": "Cystic fibrosis (CF), caused by CFTR mutations, is characterized by progressive pulmonary remodeling, particularly during bacterial infection. This pathological environment, exacerbated by altered epithelial growth, leads to thickened airway walls, inducing permanent narrowing and long-term breathing difficulties. However, what drives this adverse milieu remains unclear. Here, we identify activation of the de novo pathway of pyrimidine synthesis (DNPPS) as a central contributor of CF lung remodeling. In response to impaired mitochondrial bioenergetics, CFTR-mutant epithelial cells engage compensatory DNPPS activity, functionally coupling mitochondrial oxidative metabolism to pyrimidine production and, inadvertently, promoting proliferation. This phenotype is reversible with CFTR modulators and pharmacologic DNPPS inhibitors using clinically established agents. Strikingly, Pseudomonas aeruginosa, the predominant CF pathogen, undergoes convergent pyrimidine adaptation, activating its own DNPPS machinery to amplify biomass and sustain a remodeled niche. Together, these findings define pyrimidine metabolism as a shared host-pathogen axis driving epithelial restructuring and bacterial persistence in the CF lung.",
  "abstract_shown": true,
  "affiliations": [
    "Division of Infectious Diseases, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.",
    "Division of Gastroenterology, Hepatology, and Nutrition, Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Center for Microbial Medicine, Children's Hospital of Philadelphia, Philadelphia, PA, USA.",
    "Vagelos College of Physicians and Surgeons, Columbia University Irving Medical Center, New York, NY, USA.",
    "Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.",
    "Division of Infectious Diseases, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA. sr3302@cumc.columbia.edu."
  ],
  "article_type": "research support, non u.s. gov't",
  "arxiv": null,
  "author_total": 8,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Gaurav Kumar Lohia",
      "orcid": "0000-0002-4186-621X"
    },
    {
      "affs": [
        0
      ],
      "name": "Ying-Tsun Chen",
      "orcid": "0000-0002-2966-3153"
    },
    {
      "affs": [
        0
      ],
      "name": "Samantha Chen"
    },
    {
      "affs": [
        0
      ],
      "name": "Ayesha Beg"
    },
    {
      "affs": [
        1
      ],
      "name": "Erin Theiller"
    },
    {
      "affs": [
        2,
        3
      ],
      "name": "Aomeng Cui"
    },
    {
      "affs": [
        1
      ],
      "name": "Ahmed M Moustafa",
      "orcid": "0000-0002-9949-6936"
    },
    {
      "affs": [
        4
      ],
      "name": "Sebastián A Riquelme",
      "orcid": "0000-0002-8375-4320"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/5qtacqzg0nrhk.bib",
  "cited_by": 0,
  "doi": "10.1038/s41467-026-77940-z",
  "fulltext_url": "https://europepmc.org/articles/PMC13687554",
  "id": "5qtacqzg0nrhk",
  "issns": [
    "2041-1723"
  ],
  "landing_url": "https://europepmc.org/article/MED/42907429",
  "language": "eng",
  "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": [
    [
      "openalex",
      "2740|Cystic Fibrosis Research Advances"
    ]
  ],
  "openalex": "W7213899948",
  "pdf_url": "https://europepmc.org/articles/PMC13687554?pdf=render",
  "pmcid": "PMC13687554",
  "pmid": "42907429",
  "published": "2026-09-22",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/5qtacqzg0nrhk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:19:57Z",
      "native_id": "MED:42907429",
      "source": "europepmc",
      "url": "https://europepmc.org/article/MED/42907429"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2740|Cystic Fibrosis Research Advances",
      "subfield": "general"
    }
  ],
  "title": "Host-pathogen pyrimidine metabolism drives cystic fibrosis lung disease.",
  "title_text": "Host-pathogen pyrimidine metabolism drives cystic fibrosis lung disease.",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:19:57Z",
  "url": "https://research.draconitic.com/paper/5qtacqzg0nrhk",
  "venue": "Nature communications",
  "versions": []
}