{
  "abstract": "Bacterial genetic variation contributes to the outcome of infection, but its relationship with host immune responses is rarely investigated in the same patients, limiting the biological interpretation of pathogen-associated disease severity. Here, we integrated pathogen genomics, clinical outcomes and host transcriptomics to investigate host-pathogen interactions in melioidosis, a frequently fatal infection caused by Burkholderia pseudomallei. We analysed prospective clinical data from 2,142 patients, whole-genome sequences from 2,101 infecting isolates and 646 paired host blood transcriptomes across five cohorts collected between 2012 and 2023. Infections were typically dominated by a single strain, with limited within-host diversification, supporting the use of an infecting isolate genome to investigate pathogen-associated clinical outcomes. Bacterial genome-wide association studies identified one locus associated with binary mortality at genome-wide significance. Incorporating patient age, sex, body mass index and Charlson Comorbidity Index increased this to four, while modelling time to death as a continuous phenotype identified seven loci. Integration with paired host transcriptomes linked mortality-associated bacterial genetic variation to imputed signatures of increased immature neutrophils and reduced neutrophil degranulation. An intergenic region upstream of the polyketide synthesis locus BPSS1006-BPSS1011 was additionally associated with downregulation of host genes involved in myeloid-cell signalling and cell proliferation pathways. These findings connect naturally occurring B. pseudomallei genomic variation associated with mortality to distinct host immune signatures, providing insight into pathogen-host interactions underlying severe melioidosis and a framework for investigating the contribution of pathogen genetic diversity to clinical outcomes.",
  "abstract_shown": true,
  "affiliations": [
    "Mahidol-Oxford Tropical Medicine Research Unit, Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand"
  ],
  "article_type": "New results",
  "arxiv": null,
  "author_total": 26,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "A. Wongprommoon"
    },
    {
      "name": "P. Boonklang"
    },
    {
      "name": "K. L. Burnham"
    },
    {
      "name": "C. Chomkatekaew"
    },
    {
      "name": "K. Angchagun"
    },
    {
      "name": "G. Wongsuvan"
    },
    {
      "name": "T. Ngernseng"
    },
    {
      "name": "D. Limmathurotsakul"
    },
    {
      "name": "T. Boonchalermvichien"
    },
    {
      "name": "T. D. Coston"
    },
    {
      "name": "R. Phunpang"
    },
    {
      "name": "T. Yimthin"
    },
    {
      "name": "P. Rongkard"
    },
    {
      "name": "W. Lee"
    },
    {
      "name": "B. Kronsteiner"
    },
    {
      "name": "J. Knight"
    },
    {
      "name": "J. Corander"
    },
    {
      "name": "S. J. Peacock"
    },
    {
      "name": "J. Parkhill"
    },
    {
      "name": "N. P. J. Day"
    },
    {
      "name": "S. J. Dunachie"
    },
    {
      "name": "T. E. West"
    },
    {
      "name": "N. Chantratita"
    },
    {
      "name": "N. R. Thomson"
    },
    {
      "name": "E. E. Davenport"
    },
    {
      "name": "C. Chewapreecha"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/amtzbv8nm6ev5.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.11.06.764829",
  "fulltext_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764829v1.full",
  "id": "amtzbv8nm6ev5",
  "issns": [],
  "landing_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764829v1",
  "language": null,
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "biorxiv",
      "genomics"
    ]
  ],
  "openalex": null,
  "pdf_url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764829v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-11-06",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/amtzbv8nm6ev5.ris",
  "sources": [
    {
      "first_seen": "2026-11-10T00:24:51Z",
      "native_id": "10.64898/2026.11.06.764829",
      "source": "biorxiv",
      "url": "https://www.biorxiv.org/content/10.64898/2026.11.06.764829v1"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "biorxiv:genomics",
      "subfield": "genetics-genomics"
    }
  ],
  "title": "Integrating bacterial genomics and host transcriptomics links Burkholderia pseudomallei variation to melioidosis mortality and neutrophil responses",
  "title_text": "Integrating bacterial genomics and host transcriptomics links Burkholderia pseudomallei variation to melioidosis mortality and neutrophil responses",
  "type": "preprint",
  "updated_at": "2026-11-10T00:24:51Z",
  "url": "https://research.draconitic.com/paper/amtzbv8nm6ev5",
  "venue": "bioRxiv",
  "versions": []
}