Cargando…
Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans
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 Caenorhabdit...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536714/ https://www.ncbi.nlm.nih.gov/pubmed/23300454 http://dx.doi.org/10.1371/journal.ppat.1003101 |
_version_ | 1782254795469357056 |
---|---|
author | Cezairliyan, Brent Vinayavekhin, Nawaporn Grenfell-Lee, Daniel Yuen, Grace J. Saghatelian, Alan Ausubel, Frederick M. |
author_facet | Cezairliyan, Brent Vinayavekhin, Nawaporn Grenfell-Lee, Daniel Yuen, Grace J. Saghatelian, Alan Ausubel, Frederick M. |
author_sort | Cezairliyan, Brent |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3536714 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-35367142013-01-08 Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans Cezairliyan, Brent Vinayavekhin, Nawaporn Grenfell-Lee, Daniel Yuen, Grace J. Saghatelian, Alan Ausubel, Frederick M. PLoS Pathog Research Article 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. Public Library of Science 2013-01-03 /pmc/articles/PMC3536714/ /pubmed/23300454 http://dx.doi.org/10.1371/journal.ppat.1003101 Text en © 2013 Cezairliyan et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
spellingShingle | Research Article Cezairliyan, Brent Vinayavekhin, Nawaporn Grenfell-Lee, Daniel Yuen, Grace J. Saghatelian, Alan Ausubel, Frederick M. Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans |
title | Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans
|
title_full | Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans
|
title_fullStr | Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans
|
title_full_unstemmed | Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans
|
title_short | Identification of Pseudomonas aeruginosa Phenazines that Kill Caenorhabditis elegans
|
title_sort | identification of pseudomonas aeruginosa phenazines that kill caenorhabditis elegans |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3536714/ https://www.ncbi.nlm.nih.gov/pubmed/23300454 http://dx.doi.org/10.1371/journal.ppat.1003101 |
work_keys_str_mv | AT cezairliyanbrent identificationofpseudomonasaeruginosaphenazinesthatkillcaenorhabditiselegans AT vinayavekhinnawaporn identificationofpseudomonasaeruginosaphenazinesthatkillcaenorhabditiselegans AT grenfellleedaniel identificationofpseudomonasaeruginosaphenazinesthatkillcaenorhabditiselegans AT yuengracej identificationofpseudomonasaeruginosaphenazinesthatkillcaenorhabditiselegans AT saghatelianalan identificationofpseudomonasaeruginosaphenazinesthatkillcaenorhabditiselegans AT ausubelfrederickm identificationofpseudomonasaeruginosaphenazinesthatkillcaenorhabditiselegans |