Co-evolutionary signals fromBurkholderia pseudomalleigenomics identify its survival strategies and highlight improving environmental health as prevention policy

Abstract

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, of which a majority (61.5%) of signals detected in the discovery dataset can be replicated in the validation dataset (totalling 2,011 genomes). Genes under co-selection are mostly conditionally expressed with marked expression correlation of gene-gene pairs found in 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 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.

An Evolutionary Arms Race Between Burkholderia pseudomallei and Host Immune System: What Do We Know?

“…An experimental study further reported that a gene of inner core LPS biosynthesis cluster ( waaE: BPSL2510) is vital for a long-term water incubation ( Moore et al, 2008 ). Moreover, an adhesin BPSL1661 was identified as a hub for co-evolutionary signals in B. pseudomallei population ( Chewapreecha et al, 2020 ). The gene was functionally characterized as essential during nutrient starvation ( Chewapreecha et al, 2020 ), thereby highlighting nutrient limitation as a major evolutionary pressure experienced by this microorganism.…”

“…Moreover, an adhesin BPSL1661 was identified as a hub for co-evolutionary signals in B. pseudomallei population ( Chewapreecha et al, 2020 ). The gene was functionally characterized as essential during nutrient starvation ( Chewapreecha et al, 2020 ), thereby highlighting nutrient limitation as a major evolutionary pressure experienced by this microorganism. The presence of B. pseudomallei is strongly associated with the low-nutrient soil ( Limmathurotsakul et al, 2010b ; Hantrakun et al, 2016 ).…”

“… We estimated the proportion of infection outcome variations (survival vs. mortal outcomes after 28 days) explained by B. pseudomallei nucleotide polymorphisms (SNPs). SNPs were called from Chewapreecha et al (2019 , 2020) using kSNP v3 software. A filtering for minimum allele frequency at 0.01 (MAF = 0.01) resulted in 65,379 SNPs for the analysis.…”