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Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells

Cellular senescence is an irreversible state of proliferation arrest evoked by a myriad of stresses including oncogene activation, telomere shortening/dysfunction and genotoxic insults. It has been associated with tumor activation, immune suppression and aging, owing to the secretion of proinflammat...

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Autores principales: Secher, Thomas, Samba-Louaka, Ascel, Oswald, Eric, Nougayrède, Jean-Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792898/
https://www.ncbi.nlm.nih.gov/pubmed/24116215
http://dx.doi.org/10.1371/journal.pone.0077157
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author Secher, Thomas
Samba-Louaka, Ascel
Oswald, Eric
Nougayrède, Jean-Philippe
author_facet Secher, Thomas
Samba-Louaka, Ascel
Oswald, Eric
Nougayrède, Jean-Philippe
author_sort Secher, Thomas
collection PubMed
description Cellular senescence is an irreversible state of proliferation arrest evoked by a myriad of stresses including oncogene activation, telomere shortening/dysfunction and genotoxic insults. It has been associated with tumor activation, immune suppression and aging, owing to the secretion of proinflammatory mediators. The bacterial genotoxin colibactin, encoded by the pks genomic island is frequently harboured by Escherichia coli strains of the B2 phylogenetic group. Mammalian cells exposed to live pks+ bacteria exhibit DNA-double strand breaks (DSB) and undergo cell-cycle arrest and death. Here we show that cells that survive the acute bacterial infection with pks+ E. coli display hallmarks of cellular senescence: chronic DSB, prolonged cell-cycle arrest, enhanced senescence-associated β-galactosidase (SA-β-Gal) activity, expansion of promyelocytic leukemia nuclear foci and senescence-associated heterochromatin foci. This was accompanied by reactive oxygen species production and pro-inflammatory cytokines, chemokines and proteases secretion. These mediators were able to trigger DSB and enhanced SA-β-Gal activity in bystander recipient cells treated with conditioned medium from senescent cells. Furthermore, these senescent cells promoted the growth of human tumor cells. In conclusion, the present data demonstrated that the E. coli genotoxin colibactin induces cellular senescence and subsequently propel bystander genotoxic and oncogenic effects.
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spelling pubmed-37928982013-10-10 Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells Secher, Thomas Samba-Louaka, Ascel Oswald, Eric Nougayrède, Jean-Philippe PLoS One Research Article Cellular senescence is an irreversible state of proliferation arrest evoked by a myriad of stresses including oncogene activation, telomere shortening/dysfunction and genotoxic insults. It has been associated with tumor activation, immune suppression and aging, owing to the secretion of proinflammatory mediators. The bacterial genotoxin colibactin, encoded by the pks genomic island is frequently harboured by Escherichia coli strains of the B2 phylogenetic group. Mammalian cells exposed to live pks+ bacteria exhibit DNA-double strand breaks (DSB) and undergo cell-cycle arrest and death. Here we show that cells that survive the acute bacterial infection with pks+ E. coli display hallmarks of cellular senescence: chronic DSB, prolonged cell-cycle arrest, enhanced senescence-associated β-galactosidase (SA-β-Gal) activity, expansion of promyelocytic leukemia nuclear foci and senescence-associated heterochromatin foci. This was accompanied by reactive oxygen species production and pro-inflammatory cytokines, chemokines and proteases secretion. These mediators were able to trigger DSB and enhanced SA-β-Gal activity in bystander recipient cells treated with conditioned medium from senescent cells. Furthermore, these senescent cells promoted the growth of human tumor cells. In conclusion, the present data demonstrated that the E. coli genotoxin colibactin induces cellular senescence and subsequently propel bystander genotoxic and oncogenic effects. Public Library of Science 2013-10-08 /pmc/articles/PMC3792898/ /pubmed/24116215 http://dx.doi.org/10.1371/journal.pone.0077157 Text en © 2013 Secher 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
Secher, Thomas
Samba-Louaka, Ascel
Oswald, Eric
Nougayrède, Jean-Philippe
Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells
title Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells
title_full Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells
title_fullStr Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells
title_full_unstemmed Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells
title_short Escherichia coli Producing Colibactin Triggers Premature and Transmissible Senescence in Mammalian Cells
title_sort escherichia coli producing colibactin triggers premature and transmissible senescence in mammalian cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3792898/
https://www.ncbi.nlm.nih.gov/pubmed/24116215
http://dx.doi.org/10.1371/journal.pone.0077157
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