BurkHostGEN: a study protocol for evaluating variations in the Burkholderia pseudomallei and host genomes associated with melioidosis infection
Angchagun K., Boonklang P., Chomkatekaew C., Pakdeerat S., Wongsuwan G., Amornchai P., Wuthiekanun V., Panapipat S., Ngernseng T., Waithira N., Walton S., Limmathurotsakul D., Surawong A., Siriboon S., Chamnan P., Chantratita N., Dunachie S., Corander J., Davenport EE., Knight J., Parkhill J., Peacock SJ., Thomson NR., Day NPJ., Chewapreecha C.
Background: Melioidosis is a frequently fatal disease caused by an environmental bacterium Burkholderia pseudomallei. The disease is prevalent in northeast Thailand, particularly among rice field farmers who are at risk of bacterial exposure through contact with contaminated soil and water. However, not all exposure results in disease, and infection can have different infection outcomes. Our hypothesis is that the acquisition and outcomes of melioidosis may be influenced by genetic factors of the bacterium, the host, or a combination of both. To address this hypothesis, we aim to collect, sequence, and analyse genetic data from melioidosis patients and controls, along with isolates of B. pseudomallei obtained from patients. Additionally, we will study the metagenomics of the household water supply for both patients and controls, including the presence of B. pseudomallei. Methods: BurkHostGEN is an ongoing observational study being conducted at Sunpasitthiprasong Hospital, Ubon Ratchathani, Thailand. Weare obtaining consent from 600 melioidosis patients and 700 controls, spanning both sexes, to collect 1 mL of blood for host DNA analysis, 3 mL of blood for RNA analysis, as well as 5 L of household water supply for metagenomic analysis. Additionally, we are isolating B. pseudomallei from the melioidosis patients to obtain bacterial DNA. This comprehensive approach will allow us to identify B. pseudomallei and their paired host genetic factors associated with disease acquisition and severity. Ethical approvals have been obtained for BurkHostGEN. Host and bacterial genetic data will be uploaded to European Genome-Phenome Archive (EGA) and European Nucleotide Archive (ENA), respectively. Conclusions: BurkHostGEN holds the potential to discover bacterial and host genetic factors associated with melioidosis infection and severity of illness. It can also support various study designs, including biomarker validation, disease pathogenesis, and epidemiological analysis not only for melioidosis but also for other infectious diseases.