Abstract
Melioidosis is a highly neglected yet serious infectious disease caused by the environmental
bacterium Burkholderia pseudomallei. Previous studies have shown that healthy individuals living
in disease hotspots, such as northeast Thailand, often develop serological evidence of exposure
from early childhood. However, some individuals develop melioidosis later in life, and the disease
exhibits significant variability in its clinical presentation and severity.
We hypothesise that genetic factors in the bacteria, the host, or both contribute to this
heterogeneity in disease outcomes. Using the comprehensive database from the BurkHostGEN
cohort, supported by a Wellcome Trust award to Dr. Chewapreecha, we paired B. pseudomallei
samples with host data to investigate these genetic influences. From 2023 to 2024, we
characterised the population structure of clinical bacterial isolates. Analysis of the bacterial
population revealed three major lineages and their dissemination patterns across northeast
Thailand, findings which were recently published.*
Building on this, we conducted a genome-wide association study (GWAS) to identify bacterial
genetic variations linked to 28-day mortality in infected patients. One locus, a metal ion
transporter gene cluster (BPSL1952-BPSL1953), reached genome-wide significance. This cluster
likely facilitates metal ion acquisition under limiting conditions—such as during intracellular
survival—thereby enhancing bacterial persistence inside host cells and promoting systemic
infection, which correlates with increased host mortality.
