Decoding the triad: the interplay between Environment, Pathogen, and Host in melioidosis (DeEPH) (360G-Wellcome-323077_Z_24_Z)

Melioidosis, caused by the environmental bacterium Burkholderia pseudomallei, is a neglected tropical disease with an estimated global fatality rate of 54%. In the Lower Mekong Basin, 22% of patients die before receiving a culture- confirmed diagnosis, 26% of diagnosed patients die within a month, and 24% of one-month survivors are readmitted within a year. Disease progression – from acquisition to acute infection and recovery – is influenced by a range of bacterial, host, and environmental factors. My research in northeast Thailand has identified genetic variation in B. pseudomallei and host genes associated with clinical outcomes at distinct stages of disease progression. However, the mechanisms linking these genetic variants to the outcomes remain poorly understood. To address this knowledge gap, I will combine population genetics and multi-omic approaches to investigate how genetic variants influence molecular pathways and contribute to disease outcomes. I will also examine how environmental factors, such as exposure to contaminated soil and water, treatment timing, and patient adherence, modify risk throughout the disease trajectory. This work will enable the identification of biomarkers to stratify patient risk and inform targeted interventions to improve melioidosis outcomes, while expanding omic databases for underrepresented populations, and strengthening genetic research capacity in Thailand, Laos, and Cambodia.