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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

Demarre, G., Prudent, V., Schenk, H., Rousseau, E., Bringer, M.-A., Barnich, N., et al. (2019). The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages. PLoS Pathogens, 15(11): e1008123. doi:10.1371/journal.ppat.1008123.

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Demarre, Gaëlle, Author
Prudent, Victoria, Author
Schenk, Hanna1, Author           
Rousseau, Emilie, Author
Bringer, Marie-Agnès, Author
Barnich, Nicolas, Author
Tran Van Nhieu, Guy, Author
Rimsky, Sylvie, Author
De Monte, Silvia1, 2, Author           
Espéli, Olivier, Author
Affiliations:
1Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_1445641              
2Research Group Dynamics of Microbial Collectives, Department Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Max Planck Society, ou_3016582              

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 Abstract: Author summary Intestinal microbiome dysbiosis has been consistently described in patients with Crohn’s disease. The adherent-invasive E. coli (AIEC) pathotype in particular, has been implicated in the pathogenesis. AIEC colonize intestinal epithelial cells and survive and replicate within macrophages. Here we demonstrated that growth of AIEC LF82 inside the toxic mature phagolysosomes of macrophages requires sequential adaptations and phenotype switches. First, the stringent response halts the replicative cell cycle of AIEC LF82 for few hours. During this period a large number of AIEC LF82 acquires the ability to tolerate antibiotic treatments. Later when, AIEC multiplication restarts it requires DNA repair suggesting that AIEC have accumulated lesions during the first hours post infection. We observed that non growing bacteria appear frequently from the population of growing AIEC LF82 in this second phase. This raises the proportion of antibiotic tolerant AIEC LF82 up to 10% of the population. 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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Language(s): eng - English
 Dates: 2019-11-142019-10-032019-11-142019
 Publication Status: Issued
 Pages: -
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 Table of Contents: -
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 Identifiers: DOI: 10.1371/journal.ppat.1008123
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Title: PLoS Pathogens
  Other : PLoS Pathog.
Source Genre: Journal
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Publ. Info: San Francisco, CA : Public Library of Science
Pages: - Volume / Issue: 15 (11) Sequence Number: e1008123 Start / End Page: - Identifier: ISSN: 1553-7366
CoNE: https://pure.mpg.de/cone/journals/resource/1000000000018830