Biology subjects

Chomkatekaew, C.

Publications and source records attributed to Chomkatekaew, C..

3 recordsLinked to original sources

bioRxiv2026

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

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.

genomics↗

bioRxiv2026

A 28-year evolution experiment on Burkholderia pseudomallei survival in nutrient-depleted sterile water

Environmental persistence allows opportunistic pathogens to survive a range of harsh conditions, increasing the likelihood of eventual infection. Burkholderia pseudomallei, the causative agent of melioidosis, can endure long-term nutrient-depletion in the environment, but its adaptive mechanisms remain poorly understood. Here, we investigated the evolutionary trajectory of a clinical B. pseudomallei strain maintained in sterile water since 1994. The strain was inoculated into nine individual tubes at nine initial concentrations (102-1010 CFU/mL) and has remained viable to date. Liquid chromatography-mass spectrometry analysis of the water identified potential carbon sources, including phthalic acid -- a plastic degradation product likely leached from inoculation tubes -- which the strain can metabolise via an intact catabolic operon. Genomic variations accumulated between 1994 and 2022 were characterised using both single-colony and plate-sweep sequencing which provided complementary insights. Across all tubes, we identified 249 single-nucleotide polymorphisms (SNPs), 73 indels, and a large-scale deletion. Cultures from each tube displayed a consistently low mutation rate (3.18 x 10- SNPs per site per year), suggesting that cells entered a dormant or slow-growth state. Of 393 genes with mutations, 193 were independently mutated in more than one tube, particularly those involved in signal transduction, cell wall and membrane biogenesis, and secondary metabolite synthesis. These patterns indicate parallel adaptation to long-term nutrient deprivation through modulation of cell-density-related functions and loss of metabolically costly pathways. Remarkably, B. pseudomallei from this experiment remain viable after nearly three decades, providing a rare natural model for understanding how environmental bacteria endure and adapt in extremely nutrient-depleted conditions.

evolutionary biology↗

bioRxiv2023

Genetic diversity, determinants, and dissemination of Burkholderia pseudomallei lineages implicated in melioidosis in northeast Thailand

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of the disease-causing bacterial lineages, their dissemination, and adaptive mechanisms remains limited. To address this, we conducted a comprehensive genomic analysis of 1,391 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, and contemporaneous isolates from neighbouring countries, representing the most densely sampled collection to date. Our study identified three dominant lineages with unique gene sets enhancing bacterial fitness, indicating lineage-specific adaptation strategies. Crucially, recombination was found to drive lineage-specific gene flow. Transcriptome analyses of representative clinical isolates from each dominant lineage revealed heightened expression of lineage-specific genes in environmental versus infection conditions, notably under nutrient depletion, highlighting environmental persistence as a key factor in the success of dominant lineages. The study also revealed the role of environmental factors - slope of terrain, altitude, direction of rivers, and the northeast monsoons - in shaping B. pseudomallei geographical dispersal. Collectively, our findings highlight persistence in the environment as a pivotal element facilitating B. pseudomallei spread, and as a prelude to exposure and infection, thereby providing useful insights for informing melioidosis prevention and control strategies.

microbiology↗