Pseudomonas aeruginosa PAO1 kills Caenorhabditis elegans by cyanide poisoning

• Published in: Journal of bacteriology Vol. 183; no. 21; pp. 6207 - 6214
• Main Authors: Gallagher, L A, Manoil, C
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01.11.2001
• Subjects: Animals; Bacteria; Bacteriology; Caenorhabditis elegans; Caenorhabditis elegans - drug effects; Caenorhabditis elegans - microbiology; cyanide synthase; egl gene; Genes; hcnC gene; hcnC protein; Hydrogen Cyanide - metabolism; Hydrogen Cyanide - pharmacology; hydrogen cyanide synthase; Multienzyme Complexes - genetics; Mutation; Oxidoreductases - genetics; Oxidoreductases Acting on CH-NH2 Group Donors; Phenazines - metabolism; Physiology and Metabolism; Poisons; Pseudomonas aeruginosa; Pseudomonas aeruginosa - pathogenicity; Worms
• ISSN: 0021-9193; 1098-5530
• DOI: 10.1128/JB.183.21.6207-6214.2001

In this report we describe experiments to investigate a simple virulence model in which Pseudomonas aeruginosa PAO1 rapidly paralyzes and kills the nematode Caenorhabditis elegans. Our results imply that hydrogen cyanide is the sole or primary toxic factor produced by P. aeruginosa that is responsible for killing of the nematode. Four lines of evidence support this conclusion. 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, exposure to exogenous cyanide alone at levels comparable to the level produced by PAO1 killed nematodes with kinetics similar to those observed with bacteria. The killing was not enhanced if hcnC mutant bacteria were present during cyanide exposure. And fourth, a nematode mutant (egl-9) resistant to P. aeruginosa was also resistant to killing by exogenous cyanide in the absence of bacteria. A model for nematode killing based on inhibition of mitochondrial cytochrome oxidase is presented. The action of cyanide helps account for the unusually broad host range of virulence of P. aeruginosa and may contribute to the pathogenesis in opportunistic human infections due to the bacterium.