Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning

In this report we describe experiments to investigate a simple virulence mo del in which Pseudomonas aeruginosa PAO1 rapidly paralyzes and kills the ne matode Caenorhabditis elegans. Our results imply that hydrogen cyanide is t he sole or primary toxic factor produced by P. aeruginosa that is responsib le for killing of the nematode. Four lines of evidence support this conclus ion. First, a transposon insertion mutation in a gene encoding a subunit of hydrogen cyanide synthase (hcnC) eliminated nematode killing. Second, the 17 avirulent mutants examined all exhibited reduced cyanide synthesis, and the residual production levels correlated with killing efficiency. Third, e xposure to exogenous cyanide alone at levels comparable to the level produc ed by PAO1 killed nematodes with kinetics similar to those observed with ba cteria. The killing was not enhanced if hcnC mutant bacteria were present d uring cyanide exposure. And fourth, a nematode mutant (egl-9) resistant to P. aeruginosa was also resistant to killing by exogenous cyanide in the abs ence of bacteria. A model for nematode killing based on inhibition of mitoc hondrial cytochrome oxidase is presented. The action of cyanide helps accou nt for the unusually broad host range of virulence of P. aeruginosa and may contribute to the pathogenesis in opportunistic human infections due to th e bacterium.