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Evaluating Virulence and Pathogenesis of Aeromonas Infection in a Caenorhabditis elegans Model
Published on: December 20, 2018
Molecular mechanisms of bacterial virulence elucidated using a Pseudomonas aeruginosa-Caenorhabditis elegans
S Mahajan-Miklos1, M W Tan, L G Rahme
1Department of Genetics, Harvard Medical School, Massachusetts General Hospital, Boston 02114, USA.
Abstract:
The human opportunistic pathogen Pseudomonas aeruginosa strain PA14 kills Caenorhabditis elegans. Using systematic mutagenesis of PA14 to identify mutants that fail to kill C. elegans and a C. elegans mutant that lacks P-glycoproteins, we identified phenazines, secreted P. aeruginosa pigments, as one of the mediators of killing. Analysis of C. elegans mutants with altered responses to oxidative stress suggests that phenazines exert their toxic effects on C. elegans through the generation of reactive oxygen species. Finally, we show that phenazines and other P. aeruginosa factors required for C. elegans killing are also required for pathogenesis in plants and mice, illustrating that this model tackles the dual challenges of identifying bacterial virulence factors as well as host responses to them.
Insights
Phenazines, secreted pigments from Pseudomonas aeruginosa, cause toxicity in C. elegans by generating reactive oxygen species. These virulence factors are also crucial for pathogenesis in plants and mice.
Area of Science:
- Microbiology
- Pathogenesis
- Toxicology
Background:
- Pseudomonas aeruginosa is an opportunistic pathogen.
- Understanding bacterial virulence factors and host responses is crucial.
Purpose of the Study:
- Identify Pseudomonas aeruginosa virulence factors responsible for killing C. elegans.
- Investigate the mechanisms of toxicity and host responses.
Main Methods:
- Systematic mutagenesis of P. aeruginosa PA14.
- Utilized a C. elegans mutant lacking P-glycoproteins.
- Analyzed C. elegans mutants with altered oxidative stress responses.
Main Results:
- Phenazines, secreted P. aeruginosa pigments, were identified as key mediators of killing.
- Phenazines induce toxicity in C. elegans via reactive oxygen species generation.
- P. aeruginosa factors for C. elegans killing are conserved in plant and mouse pathogenesis.
Conclusions:
- Phenazines are significant virulence factors of P. aeruginosa.
- Reactive oxygen species play a critical role in P. aeruginosa-mediated toxicity.
- The C. elegans model effectively identifies conserved bacterial virulence factors and host responses.

