Melioidosis is a neglected tropical disease caused by the Gram-negative soil bacterium Burkholderia pseudomallei. The mortality rate of this disease is greater than 50% in regions where the bacteria is endemic, affecting more than 150,000 people per year. B. pseudomallei is resistant to many common antibacterials, and is able to enter, replicate and survive inside host cells; allowing the infection to persist and progress. The current therapeutic standard of care is prolonged and costly – lasting a minimum of 14 weeks and unaffordable to many affected with the disease.
Efforts to develop new treatments for melioidosis are hampered by the risks associated to working with pathogenic B. pseudomallei, which restricts research to facilities with Biosafety Level (BSL) 3 containment. Closely related Burkholderia species that are less pathogenic, however, have been described that can be investigated under less stringent BSL 2 containment. We hypothesized that these less pathogenic species could be used as model organisms for developing therapies that would also be effective against B. pseudomallei.
Using a microbroth dilution assay, we compared the susceptibility of three Australian B. pseudomallei isolates and five near-neighbour Burkholderia species – B. humptydooensis, B. thailandensis, B. oklahomensis, B territorii and B. stagnalis – to a panel of compounds that included antibiotics currently used to treat melioidosis, as well as broad spectrum antibacterial agents. We also compared the susceptibility profiles of the near-neighbour Burkholderia species to B. pseudomallei for over 400 compounds from the Medicines for Malaria Venture Pathogen Box.
From these comparisons, we observed a high degree of similarity in the level of susceptibility of B. pseudomallei and the less pathogenic near-neighbour species, B. humptydooensis, B. thailandensis, B. oklahomensis and B. territorii. From this, we conclude that less pathogenic species of Burkholderia are excellent model organisms for developing new anti-melioidosis therapies.The lower risk-group classification of these near-neighbour species compared to B. pseudomallei means that more laboratories have adequate facilities to perform the initial investigations toward developing new compounds for treating melioidosis.