{
  "abstract": "Pneumococcal meningitis is the most common form of bacterial meningitis, with high case fatality rates. Bacterial genetics influence disease severity, but the underlying mechanisms remain poorly understood. Here, we evaluated top variants from a genome-wide association study (GWAS) linking Streptococcus pneumoniae genetic variation to disease outcome. Fifteen S. pneumoniae knockout mutants were tested for virulence in a zebrafish embryo meningitis model; six showed reduced virulence compared to wild-type, but four were excluded following competitive index and growth assays. Loss of SPV_1044 (lacR) and SPV_1393 (trxB) resulted in lower bacterial loads, impaired neuroinvasion and a reduced inflammatory response. Furthermore, deletion of lacR, encoding a regulator of galactose metabolism, led to delayed growth in galactose and human cerebrospinal fluid. Deletion of trxB, encoding thioredoxin reductase, increased susceptibility to oxidative stress. This proof-of-concept study, combining pathogen GWAS with in vivo validation, identifies two pneumococcal virulence genes linked to disease severity.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Neurology, Amsterdam UMC location University of Amsterdam, Amsterdam Neuroscience, Amsterdam, The Netherlands",
    "Department of Medical Microbiology and Infection Prevention, Amsterdam UMC location VU Universiteit Amsterdam, Amsterdam, The Netherlands",
    "Department of Fundamental Microbiology, Faculty of Biology and Medicine, University of Lausanne, Lausanne, Switzerland",
    "Department of Neurology, Leiden University Medical Center, Leiden University, Leiden, The Netherlands",
    "The Centre for Human Drug Research, Leiden, The Netherlands",
    "European Molecular Biology Laboratory, European Bioinformatics Institute EMBL-EBI, Hinxton, Cambridgeshire UK",
    "The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK",
    "Department of Clinical Epidemiology and Biostatistics, Amsterdam UMC location University of Amsterdam, Amsterdam, The Netherlands",
    "Department of Clinical Epidemiology, Infectious Diseases Surveillance and Epidemiology, Aarhus University, Aarhus, Denmark"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 16,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Rutger Koning"
    },
    {
      "affs": [
        0,
        1,
        2
      ],
      "name": "Kin Ki Jim"
    },
    {
      "affs": [
        3,
        4
      ],
      "name": "Philip H. C. Kremer"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "Hsueh-Chien Raymond Cheng"
    },
    {
      "affs": [
        0
      ],
      "name": "Valery Jaspers"
    },
    {
      "affs": [
        0
      ],
      "name": "Mans Perez"
    },
    {
      "affs": [
        0,
        7
      ],
      "name": "Bart Ferwerda"
    },
    {
      "affs": [
        2
      ],
      "name": "Bevika Sewgoolam"
    },
    {
      "affs": [
        1
      ],
      "name": "Roy Ummels"
    },
    {
      "affs": [
        1
      ],
      "name": "Maikel Boot",
      "orcid": "0000-0002-9734-6475"
    },
    {
      "affs": [
        5,
        6
      ],
      "name": "John A. Lees",
      "orcid": "0000-0001-5360-1254"
    },
    {
      "affs": [
        6
      ],
      "name": "Stephen D. Bentley",
      "orcid": "0000-0001-8094-3751"
    },
    {
      "affs": [
        2
      ],
      "name": "Jan-Willem Veening",
      "orcid": "0000-0002-3162-6634"
    },
    {
      "affs": [
        1,
        8
      ],
      "name": "Christina M.J.E. Vandenbroucke-Grauls"
    },
    {
      "affs": [
        0
      ],
      "name": "Matthijs C. Brouwer"
    },
    {
      "affs": [
        0
      ],
      "name": "Diederik van de Beek",
      "orcid": "0000-0002-4571-044X"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/erm91yhcd0s03.bib",
  "cited_by": 1,
  "doi": "10.1038/s42003-026-10638-6",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13724663/",
  "id": "erm91yhcd0s03",
  "issns": [
    "2399-3642"
  ],
  "landing_url": "https://doi.org/10.1038/s42003-026-10638-6",
  "language": "en",
  "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": [
    [
      "heading",
      "Article"
    ],
    [
      "openalex",
      "2404|Bacterial Infections and Vaccines"
    ]
  ],
  "openalex": "W7167689683",
  "pdf_url": "https://www.nature.com/articles/s42003-026-10638-6_reference.pdf",
  "pmcid": "PMC13724663",
  "pmid": "42420622",
  "published": "2026-07-08",
  "publisher": "Nature Publishing Group",
  "ris": "https://research.draconitic.com/paper/erm91yhcd0s03.ris",
  "sources": [
    {
      "first_seen": "2026-11-04T12:23:12Z",
      "native_id": "PMC13724663",
      "source": "pmc",
      "url": "https://doi.org/10.1038/s42003-026-10638-6"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "openalex:2404|Bacterial Infections and Vaccines",
      "subfield": "microbiology"
    }
  ],
  "title": "LacR and TrxB are key virulence factors involved in pneumococcal meningitis as identified by a genome-wide association study",
  "title_text": "LacR and TrxB are key virulence factors involved in pneumococcal meningitis as identified by a genome-wide association study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-04T12:23:12Z",
  "url": "https://research.draconitic.com/paper/erm91yhcd0s03",
  "venue": "Communications Biology",
  "versions": []
}