Genetic diversity, determinants, and dissemination ofBurkholderia pseudomalleilineages implicated in melioidosis in northeast Thailand

Abstract

Melioidosis is an often-fatal neglected tropical disease caused by an environmental bacterium Burkholderia pseudomallei. However, our understanding of disease-causing bacterial lineages, dissemination, and their adaptive mechanisms remains limited. To address this, we conducted comprehensive genomic analysis of 1,265 B. pseudomallei isolates collected from nine hospitals in northeast Thailand between 2015 and 2018, presenting the most densely sampled collection to date. Our study identified four dominant lineages with unique gene sets enhancing bacterial fitness, indicating lineage-specific co-colonisation strategies. Crucially, recombination was found to drive lineage-specific gene flow. Transcriptome analysis of a representative isolate from one lineage revealed upregulation of lineage-specific genes under nutrient-depletion. Our study also demonstrated the impact of river systems, monsoons, and typhoons in shaping the geographical dispersal of B. pseudomallei. Collectively, our findings underscore the importance of bacterial persistence in the environment as a prelude to exposure and infection, thereby providing insights for melioidosis prevention and control strategies.

BurkHostGEN: a study protocol for evaluating variations in the Burkholderia pseudomallei and host genomes associated with melioidosis infection

“…Given different units of genetic variations (gene presence, unitig, and SNP), and a binary disease outcomes (estimated 30% mortality), we used an additive model 32 to calculate the sample size with different MAF. Using a genome-wide significant cut-off at 5 × 10 -8 and genotype relative risk of 1.5, our combined size of over 2,400 B. pseudomallei genomes collected in the same endemic area under this study and those reported in 6 , 30 , 33 has sufficient power to detect associations with MAF of 0.15 ( Figure 2c ).…”