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The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages

Adherent Invasive Escherichia coli (AIEC) strains recovered from Crohn's disease lesions survive and multiply within macrophages. A reference strain for this pathovar, AIEC LF82, forms microcolonies within phagolysosomes, an environment that prevents commensal E. coli multiplication. Little is...

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Autores principales: Demarre, Gaëlle, Prudent, Victoria, Schenk, Hanna, Rousseau, Emilie, Bringer, Marie-Agnès, Barnich, Nicolas, Tran Van Nhieu, Guy, Rimsky, Sylvie, De Monte, Silvia, Espéli, Olivier
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855411/
https://www.ncbi.nlm.nih.gov/pubmed/31725806
http://dx.doi.org/10.1371/journal.ppat.1008123
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author Demarre, Gaëlle
Prudent, Victoria
Schenk, Hanna
Rousseau, Emilie
Bringer, Marie-Agnès
Barnich, Nicolas
Tran Van Nhieu, Guy
Rimsky, Sylvie
De Monte, Silvia
Espéli, Olivier
author_facet Demarre, Gaëlle
Prudent, Victoria
Schenk, Hanna
Rousseau, Emilie
Bringer, Marie-Agnès
Barnich, Nicolas
Tran Van Nhieu, Guy
Rimsky, Sylvie
De Monte, Silvia
Espéli, Olivier
author_sort Demarre, Gaëlle
collection PubMed
description Adherent Invasive Escherichia coli (AIEC) strains recovered from Crohn's disease lesions survive and multiply within macrophages. A reference strain for this pathovar, AIEC LF82, forms microcolonies within phagolysosomes, an environment that prevents commensal E. coli multiplication. Little is known about the LF82 intracellular growth status, and signals leading to macrophage intra-vacuolar multiplication. We used single-cell analysis, genetic dissection and mathematical models to monitor the growth status and cell cycle regulation of intracellular LF82. We found that within macrophages, bacteria may replicate or undergo non-growing phenotypic switches. This switch results from stringent response firing immediately after uptake by macrophages or at later stages, following genotoxic damage and SOS induction during intracellular replication. Importantly, non-growers resist treatment with various antibiotics. Thus, intracellular challenges induce AIEC LF82 phenotypic heterogeneity and non-growing bacteria that could provide a reservoir for antibiotic-tolerant bacteria responsible for relapsing infections.
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spelling pubmed-68554112019-11-22 The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages Demarre, Gaëlle Prudent, Victoria Schenk, Hanna Rousseau, Emilie Bringer, Marie-Agnès Barnich, Nicolas Tran Van Nhieu, Guy Rimsky, Sylvie De Monte, Silvia Espéli, Olivier PLoS Pathog Research Article Adherent Invasive Escherichia coli (AIEC) strains recovered from Crohn's disease lesions survive and multiply within macrophages. A reference strain for this pathovar, AIEC LF82, forms microcolonies within phagolysosomes, an environment that prevents commensal E. coli multiplication. Little is known about the LF82 intracellular growth status, and signals leading to macrophage intra-vacuolar multiplication. We used single-cell analysis, genetic dissection and mathematical models to monitor the growth status and cell cycle regulation of intracellular LF82. We found that within macrophages, bacteria may replicate or undergo non-growing phenotypic switches. This switch results from stringent response firing immediately after uptake by macrophages or at later stages, following genotoxic damage and SOS induction during intracellular replication. Importantly, non-growers resist treatment with various antibiotics. Thus, intracellular challenges induce AIEC LF82 phenotypic heterogeneity and non-growing bacteria that could provide a reservoir for antibiotic-tolerant bacteria responsible for relapsing infections. Public Library of Science 2019-11-14 /pmc/articles/PMC6855411/ /pubmed/31725806 http://dx.doi.org/10.1371/journal.ppat.1008123 Text en © 2019 Demarre 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Demarre, Gaëlle
Prudent, Victoria
Schenk, Hanna
Rousseau, Emilie
Bringer, Marie-Agnès
Barnich, Nicolas
Tran Van Nhieu, Guy
Rimsky, Sylvie
De Monte, Silvia
Espéli, Olivier
The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
title The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
title_full The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
title_fullStr The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
title_full_unstemmed The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
title_short The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
title_sort crohn’s disease-associated escherichia coli strain lf82 relies on sos and stringent responses to survive, multiply and tolerate antibiotics within macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6855411/
https://www.ncbi.nlm.nih.gov/pubmed/31725806
http://dx.doi.org/10.1371/journal.ppat.1008123
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