Drug susceptibility profiling of Australian Burkholderia species as models for developing melioidosis therapeutics

Abstract

SynopsisO_ST_ABSBackgroundC_ST_ABSMelioidosis is a neglected tropical disease caused by the Gram-negative soil bacterium Burkholderia pseudomallei. Current treatment regimens are prolonged and costly, and acquired antimicrobial resistance has been reported for all currently used antibiotics. ObjectivesEfforts to develop new treatments for melioidosis are hampered by the risks associated with handling pathogenic B. pseudomallei, which restricts research to facilities with Biosafety Level (BSL) 3 containment. Closely related Burkholderia species that are less pathogenic can be investigated under less stringent BSL 2 containment. We hypothesized that near-neighbour Burkholderia species could be used as model organisms for developing therapies that would also be effective against B. pseudomallei. MethodsWe used microbroth dilution assays to compare 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 antibiotics currently used to treat melioidosis, and general-use antibacterial agents. We also established the susceptibility profiles of B. humptydooensis and B. territorii to 400 compounds from the Medicines for Malaria Venture Pathogen Box. ResultsFrom these comparisons, we observed a high degree of similarity in the susceptibility profiles of B. pseudomallei and near-neighbour species B. humptydooensis, B. thailandensis, B. oklahomensis and B. territorii. ConclusionsLess pathogenic Australian Burkholderia species B. humptydooensis, B. thailandensis, B. oklahomensis and B. territorii are excellent model organisms for developing potential new therapies for melioidosis.