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The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS
Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 ca...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2011
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245244/ https://www.ncbi.nlm.nih.gov/pubmed/22216178 http://dx.doi.org/10.1371/journal.pone.0029113 |
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author | Mikkelsen, Helga McMullan, Rachel Filloux, Alain |
author_facet | Mikkelsen, Helga McMullan, Rachel Filloux, Alain |
author_sort | Mikkelsen, Helga |
collection | PubMed |
description | Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 carries pathogenicity islands that are absent in PAO1, the presence or absence of specific gene clusters is not predictive of virulence. Here, we show that the virulent strain PA14 has an acquired mutation in the ladS gene. This mutation has a deleterious impact on biofilm, while it results in elevated type III secretion system (T3SS) activity and increased cytotoxicity towards mammalian cells. These phenotypes can be reverted by repairing the ladS mutation on the PA14 genome. The RetS/LadS/GacS signaling cascade is associated with virulence and the switch between acute and chronic infections. RetS is a sensor that down-regulates biofilm formation and up-regulates the T3SS. Mutations in retS are acquired in strains isolated from chronically infected cystic fibrosis patients and lead to hyperbiofilm formation and reduced cytotoxicity. Conversely, the LadS sensor promotes biofilm formation and represses the T3SS. We conclude that the ladS mutation is partly responsible for the high cytotoxicity of PA14, and our findings corroborate the central role of RetS and LadS in the switch between acute and chronic infections. Given the extensive use of the reference strain PA14 in infection and virulence models, the bias caused by the ladS mutation on the observed phenotypes will be crucial to consider in future research. |
format | Online Article Text |
id | pubmed-3245244 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-32452442012-01-03 The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS Mikkelsen, Helga McMullan, Rachel Filloux, Alain PLoS One Research Article Pseudomonas aeruginosa is a pathogen that causes acute and chronic infections in a variety of hosts. The pathogenic potential of P. aeruginosa is strain-dependent. PA14 is a highly virulent strain that causes disease in a wide range of organisms, whereas PAO1 is moderately virulent. Although PA14 carries pathogenicity islands that are absent in PAO1, the presence or absence of specific gene clusters is not predictive of virulence. Here, we show that the virulent strain PA14 has an acquired mutation in the ladS gene. This mutation has a deleterious impact on biofilm, while it results in elevated type III secretion system (T3SS) activity and increased cytotoxicity towards mammalian cells. These phenotypes can be reverted by repairing the ladS mutation on the PA14 genome. The RetS/LadS/GacS signaling cascade is associated with virulence and the switch between acute and chronic infections. RetS is a sensor that down-regulates biofilm formation and up-regulates the T3SS. Mutations in retS are acquired in strains isolated from chronically infected cystic fibrosis patients and lead to hyperbiofilm formation and reduced cytotoxicity. Conversely, the LadS sensor promotes biofilm formation and represses the T3SS. We conclude that the ladS mutation is partly responsible for the high cytotoxicity of PA14, and our findings corroborate the central role of RetS and LadS in the switch between acute and chronic infections. Given the extensive use of the reference strain PA14 in infection and virulence models, the bias caused by the ladS mutation on the observed phenotypes will be crucial to consider in future research. Public Library of Science 2011-12-22 /pmc/articles/PMC3245244/ /pubmed/22216178 http://dx.doi.org/10.1371/journal.pone.0029113 Text en Mikkelsen 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 Mikkelsen, Helga McMullan, Rachel Filloux, Alain The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS |
title | The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS
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title_full | The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS
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title_fullStr | The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS
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title_full_unstemmed | The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS
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title_short | The Pseudomonas aeruginosa Reference Strain PA14 Displays Increased Virulence Due to a Mutation in ladS
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title_sort | pseudomonas aeruginosa reference strain pa14 displays increased virulence due to a mutation in lads |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3245244/ https://www.ncbi.nlm.nih.gov/pubmed/22216178 http://dx.doi.org/10.1371/journal.pone.0029113 |
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