Burkholderia pseudomallei kills the nematode Caenorhabditis elegans using an endotoxin-mediated paralysis

We investigated a non-mammalian host model system for fitness in genetic sc reening for virulence-attenuating mutations in the potential biowarfare age nts Burkholderia pseudomallei and Burkholderia mallei. We determined that B . pseudomallei is able to cause 'disease-like' symptoms and kill the nemato de Caenorhabditis elegans. Analysis of killing in the surrogate disease mod el with B. pseudomallei mutants indicated that killing did not require lipo polysaccharide (LPS) O-antigen, aminoglycoside/macrolide efflux pumping, ty pe II pathway-secreted exoenzymes or motility. Burkholderia thailandensis a nd some strains of Burkholderia cepacia also killed nematodes. Manipulation of the nematode host genotype suggests that the neuromuscular intoxication caused by both B. pseudomallei and B. thailandensis acts in part through a disruption of normal Ca2+ signal transduction. Both species produce a UV-s ensitive, gamma-irradiation-resistant, limited diffusion, paralytic agent a s part of their nematode pathogenic mechanism. The results of this investig ation suggest that killing by B. pseudomallei is an active process in C. el egans, and that the C. elegans model might be useful for the identification of vertebrate animal virulence factors in B. pseudomallei.