Synopsis 23Background: Melioidosis is a neglected tropical disease caused by the Gram-negative soil 24 bacterium Burkholderia pseudomallei. Current treatment regimens are prolonged and costly, 25 and acquired antimicrobial resistance has been reported for all currently used antibiotics. 26 Objectives: Efforts to develop new treatments for melioidosis are hampered by the risks 27 associated with handling pathogenic B. pseudomallei, which restricts research to facilities with 28 Biosafety Level (BSL) 3 containment. Closely related Burkholderia species that are less 29 pathogenic can be investigated under less stringent BSL 2 containment. We hypothesized that 30 near-neighbour Burkholderia species could be used as model organisms for developing 31 therapies that would also be effective against B. pseudomallei. 32 Methods: We used microbroth dilution assays to compare the susceptibility of three Australian 33 B. pseudomallei isolates and five near-neighbour Burkholderia species -B. humptydooensis, 34 B. thailandensis, B. oklahomensis, B territorii and B. stagnalis -to antibiotics currently used 35 to treat melioidosis, and general-use antibacterial agents. We also established the susceptibility 36 profiles of B. humptydooensis and B. territorii to 400 compounds from the Medicines for 37 Malaria Venture Pathogen Box. 38 Results: From these comparisons, we observed a high degree of similarity in the susceptibility 39 profiles of B. pseudomallei and near-neighbour species B. humptydooensis, B. thailandensis, 40 B. oklahomensis and B. territorii. 41 Conclusions: Less pathogenic Australian Burkholderia species B. humptydooensis, B. 42 thailandensis, B. oklahomensis and B. territorii are excellent model organisms for developing 43 potential new therapies for melioidosis.