Comparing the genome of a deadly bacterium isolated from patients and their environment

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Burkholderia pseudomallei is an environmental Gram-negative bacillus and the cause of melioidosis, a serious yet neglected infectious disease that is globally distributed in tropical countries. Meliodosis has been estimated to affect 165,000 people and lead to 89,000 deaths (54%) per year. Human melioidosis occurs as a result of inoculation, inhalation, and ingestion of the organism. Populations living in regions where melioidosis is endemic are repeatedly exposed to the bacterium but do not necessary develop disease. This has led to a long-standing scientific question (which is partly answered by our study) as to whether some strains are more likely to cause disease than others.

In this study, we addressed the genetic differences between isolates cultured from melioidosis patients and isolates detected in the environment. We used whole genome sequencing of 753 contemporaneous isolates obtained from infected patients (n=325) and from household drinking water supplies (n = 428) of patients and control participants living in Ubon Ratchathani, Northeast Thailand. The collection was isolated as part of a project conducted by Direk Limmathurotsakul (2010-2011) to understand behaviours that put individuals at higher risk of acquiring melioidosis. This provided bacterial isolates and metadata used in this genetic study, which is published 8 years later.

Behind the isolation of the 753 sequenced isolates was an incredible team of nurses and lab staff. Mayura Malasit and Pornpan Suntornsut approached patients right after their positive culture was confirmed. Our nurses would ask patients in Thai-Esan dialect (widely spoken in Northeast Thailand) to find out what happened to them prior to the infection. Each infection had a unique story, ranging from drinking cool-and-fresh water from a borehole by their rice paddy field to accidentally falling into a muddy pool after being chased by their buffalo pet. Buffaloes and dogs have equal status as pets for rural Thai farmers. Following patient interviews, our lab team led by Gumphol Wongsuwan and Areeya Faosap then arranged patient house visits to collect five litres of household drinking water. Although villagers were friendly, many roads in Ubon Ratchathani were still rough or muddy or both. Thanks to Gumphol’s professional driving and diplomatic skill!

Our genetic results suggest that not all exposure events to B. pseudomallei led to infection. The development of disease likely requires additional factors involving B. pseudomallei, the human host and their environment. Moreover, we identified 47 bacterial genes associated with disease or environmental isolates from Northeast Thailand and outlined the evolutionary trajectory of these genes through elevated sequence diversity and frequent gene gain and loss events. We hope this will ultimately inform vaccine design by targeting the bacteria that are more likely cause disease.

Claire Chewapreecha

Wellcome International Intermediate Fellow, Mahidol-Oxford Tropical Research Unit & King Mongkut University of Technology Thonburi