Macrophage and <it>Galleria mellonella </it>infection models reflect the virulence of naturally occurring isolates of <it>B. pseudomallei</it>, <it>B. thailandensis </it>and <it>B. oklahomensis</it>

<p>Abstract</p> <p>Background</p> <p><it>Burkholderia pseudomallei </it>is the causative agent of melioidosis, a tropical disease of humans with a variable and often fatal outcome. In murine models of infection, different strains exhibit varying degrees of virulence. In contrast, two related species, <it>B. thailandensis </it>and <it>B. oklahomensis</it>, are highly attenuated in mice. Our aim was to determine whether virulence in mice is reflected in macrophage or wax moth larvae (<it>Galleria mellonella</it>) infection models.</p> <p>Results</p> <p><it>B. pseudomallei </it>strains 576 and K96243, which have low median lethal dose (MLD) values in mice, were able to replicate and induce cellular damage in macrophages and caused rapid death of <it>G. mellonella</it>. In contrast, <it>B. pseudomallei </it>strain 708a, which is attenuated in mice, showed reduced replication in macrophages, negligible cellular damage and was avirulent in <it>G. mellonella </it>larvae. <it>B. thailandensis </it>isolates were less virulent than <it>B. pseudomallei </it>in all of the models tested. However, we did record strain dependent differences. <it>B. oklahomensis </it>isolates were the least virulent isolates. They showed minimal ability to replicate in macrophages, were unable to evoke actin-based motility or to form multinucleated giant cells and were markedly attenuated in <it>G. mellonella </it>compared to <it>B. thailandensis</it>.</p> <p>Conclusions</p> <p>We have shown that the alternative infection models tested here, namely macrophages and <it>Galleria mellonella</it>, are able to distinguish between strains of <it>B. pseudomallei</it>, <it>B. thailandensis </it>and <it>B. oklahomensis </it>and that these differences reflect the observed virulence in murine infection models. Our results indicate that <it>B. oklahomensis </it>is the least pathogenic of the species investigated. They also show a correlation between isolates of <it>B. thailandensis </it>associated with human infection and virulence in macrophage and <it>Galleria </it>infection models.</p>