Co-evolutionary signals from Burkholderia pseudomallei population genomics highlight its survival strategy in a hostile environment

The soil bacterium Burkholderia pseudomallei is the causative agent of melioidosis and a significant cause of human morbidity and mortality in many tropical and sub-tropical countries. The species notoriously survives harsh environmental conditions but the genetic architecture for these adaptations remains unclear. Here we employed a powerful combination of genome-wide epistasis and co-selection studies, gene expression analysis, and gene knockout assays to uncover genetic markers that have been repeatedly selected through B. pseudomallei evolution. These enabled us to identify a large number of mutation pairs under co-selection in distinct genes and non-coding RNA. Genes under co-selection are mostly conditionally expressed with a marked correlation in the expression of gene-gene pairs when grown under physical stress conditions. We discovered a putative adhesin (BPSL1661) as a hub of co-selection signals and experimentally confirmed the essential role of BPSL1661 under nutrient deprivation. The gene co-selection network surrounding BPSL1661 likely offers B. pseudomallei a selective advantage to survive nutrient limited conditions. We propose that anthropogenic activities such as pre- and post-harvest crop residue burning have accelerated soil nutrient depletion and may have directly contributed to the preferential survival of B. pseudomallei over other relatively benign soil microorganisms. This is expected to lead to a consequent increase in the incidence of melioidosis should the slash-and-burn practices continue to expand.