AbstractBurkholderia pseudomallei is the causative agent of melioidosis, an emerging tropical disease of high mortality. Sub-Saharan Africa represents potential melioidosis "hotspots"; however, to date, only a few cases have been reported. Here in, we compared the inflammatory patterns induced by a B. pseudomallei strain recently isolated from a fatal Gabonese case with the Thai reference strain B. pseudomallei-1026b and Burkholderia thailandensis-E264. Ex vivo, no differences were observed in terms of cellular responsiveness between strains. However, when compared with the B. pseudomallei-1026b strain, the Gabonese isolate was significantly less virulent in terms of bacterial dissemination, inflammatory response, and organ damage in mice. Genomic comparison between strains showed differences in regions containing a fimbriae/adhesion virulence protein. In addition to a lack of microbiology facilities, differences in virulence of Burkholderia strains might contribute to the diverse global clinical occurrence of melioidosis.