Integrating bacterial genomics and host transcriptomics links Burkholderia pseudomallei variation to melioidosis mortality and neutrophil responses

A genome-wide association analysis in 2,101 Burkholderia pseudomallei isolates from 2,142 melioidosis patients links bacterial genetic variation to mortality, with one locus reaching genome-wide significance.

• Why it matters: Pathogen genetic effects on disease severity are hard to interpret because host immune responses are seldom measured in the same patients, limiting biological insight into fatal melioidosis.
• What they did: The study integrated whole-genome sequences, prospective clinical outcomes, and 646 paired blood transcriptomes from five cohorts (2012–2023), using GWAS for binary death and time-to-death phenotypes.
• The result: Mortality-linked bacterial variants were associated with host signatures of increased immature neutrophils and reduced neutrophil degranulation, and an intergenic region upstream of BPSS1006-BPSS1011 was linked to downregulation of myeloid-cell signalling and cell proliferation pathways.

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