Genetic variation associated with infection and the environment in the accidental pathogenBurkholderia pseudomallei

The environmental bacterium Burkholderia pseudomallei causes melioidosis, an endemic disease in tropical and sub-tropical countries. This bacterium occupies broad ecological niches ranging from soil, contaminated water, single-cell microbes and plants to human infection. Here, we performed genome-wide association studies for genetic determinants of environmental and human adaptation using a combined dataset of 1,011 whole genome sequences of B. pseudomallei from Northeast Thailand (discovery cohort, number of clinical isolates = 325, environmental isolates =428) and Australia (validation cohort, number of clinical isolates = 185, environmental isolates = 73), representing two major global disease hotspots. With these data, we (i) identified 47 genes from 26 distinct loci associated with clinical or environmental isolates from Thailand and replicated 13 loci in an independent Australian cohort; (ii) outlined the selective pressures on the genetic loci (dN/dS) and the frequency at which they had been gained or lost throughout their evolutionary history, reflecting the bacterial adaptability to a wide range of ecological niches; and (iii) highlighted loci implicated in human disease.