Molecular mechanisms of bacterial virulence elucidated using a Pseudomonasaeruginosa Caenorhabditis elegans pathogenesis model

The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills C aenorhabditis elegans. Using systematic mutagenesis of PA14 to identify mut ants that fail to kill C. elegans and a C. elegans mutant that lacks P-glyc oproteins, we identified phenazines, secreted P. aeruginosa pigments, as on e of the mediators of killing. Analysis of C. elegans mutants with altered responses to oxidative stress suggests that phenazines exert their toxic ef fects on C. elegans through the generation of reactive oxygen species. Fina lly, we show that phenazines and other P. aeruginosa factors required for C . elegans killing are also required for pathogenesis in plants and mice, il lustrating that this model tackles the dual challenges of identifying bacte rial virulence factors as well as host responses to them.