Identification of Pseudomonas aeruginosa phenazines that kill Caenorhabditis elegans
| Autor: | Frederick M. Ausubel, Daniel Grenfell-Lee, Alan Saghatelian, Nawaporn Vinayavekhin, Brent O. Cezairliyan, Grace J. Yuen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
lcsh:Immunologic diseases. Allergy
Host–pathogen interaction Immunology Phenazine Bacterial Toxins Toxic Agents Pathogenesis medicine.disease_cause Toxicology Microbiology 03 medical and health sciences chemistry.chemical_compound Pyocyanin Virology Genetics medicine Bacteriology Animals Gram Negative Pseudomonas Infections Caenorhabditis elegans Molecular Biology Pathogen Biology Microbial Pathogens lcsh:QH301-705.5 030304 developmental biology 0303 health sciences biology 030306 microbiology Pseudomonas aeruginosa biology.organism_classification 3. Good health Bacterial Pathogens Bacterial Biochemistry Host-Pathogen Interaction chemistry lcsh:Biology (General) Pyocyanine Phenazines Parasitology lcsh:RC581-607 Bacteria Research Article |
| Zdroj: | PLoS Pathogens, Vol 9, Iss 1, p e1003101 (2013) PLoS Pathogens |
| ISSN: | 1553-7374 1553-7366 |
| Popis: | Pathogenic microbes employ a variety of methods to overcome host defenses, including the production and dispersal of molecules that are toxic to their hosts. Pseudomonas aeruginosa, a Gram-negative bacterium, is a pathogen of a diverse variety of hosts including mammals and the nematode Caenorhabditis elegans. In this study, we identify three small molecules in the phenazine class that are produced by P. aeruginosa strain PA14 that are toxic to C. elegans. We demonstrate that 1-hydroxyphenazine, phenazine-1-carboxylic acid, and pyocyanin are capable of killing nematodes in a matter of hours. 1-hydroxyphenazine is toxic over a wide pH range, whereas the toxicities of phenazine-1-carboxylic acid and pyocyanin are pH-dependent at non-overlapping pH ranges. We found that acidification of the growth medium by PA14 activates the toxicity of phenazine-1-carboxylic acid, which is the primary toxic agent towards C. elegans in our assay. Pyocyanin is not toxic under acidic conditions and 1-hydroxyphenazine is produced at concentrations too low to kill C. elegans. These results suggest a role for phenazine-1-carboxylic acid in mammalian pathogenesis because PA14 mutants deficient in phenazine production have been shown to be defective in pathogenesis in mice. More generally, these data demonstrate how diversity within a class of metabolites could affect bacterial toxicity in different environmental niches. Author Summary The bacterium Pseudomonas aeruginosa is a pathogen of a wide variety of organisms. It has been shown that P. aeruginosa factors that are critical for its toxicity to the nematode worm Caenorhabditis elegans are also important for its pathogenicity in mammals. In this report we show that phenazines, a class of small molecules produced by P. aeruginosa, act as lethal toxins against the worm. Under conditions relevant to mammalian pathogenesis, we identified one phenazine, phenazine-1-carboxylic acid, that is primarily responsible for killing worms. We found that the toxicity of this phenazine and one other phenazine, pyocyanin, are dependent on the pH of the media. We also identified a third toxic phenazine, 1-hydroxyphenazine, whose toxicity is not dependent on pH. These results show that the diversity of toxic molecules produced and released by P. aeruginosa may serve the bacterium to facilitate pathogenicity in a variety of environments. |
| Databáze: | OpenAIRE |
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