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

English version

Autoři: Gaëlle Demarre ^aff001; Victoria Prudent ^aff001; Hanna Schenk ^aff003; Emilie Rousseau ^aff001; Marie-Agnès Bringer ^aff005; Nicolas Barnich ^aff006; Guy Tran Van Nhieu ^aff001; Sylvie Rimsky ^aff001; Silvia De Monte ^aff003; Olivier Espéli ^aff001
Působiště autorů: CIRB–Collège de France, CNRS-UMR724, INSERM U1050, PSL Research University, Paris, France ^aff001; Inovarion, Paris, France ^aff002; Department of Evolutionary Theory, Max Planck Institute for Evolutionary Biology, Plön, Germany ^aff003; Institut de Biologie de l’Ecole Normale Supérieure, Département de Biologie, Ecole Normale Supérieure, CNRS, INSERM, PSL Research University, Paris, France ^aff004; Centre des Sciences du Goût et de l'Alimentation, AgroSup Dijon, CNRS, INRA, Université Bourgogne Franche-Comté, Dijon, France ^aff005; Microbes, Intestin, Inflammation et Susceptibilité de l'Hôte, UMR Inserm/Université Clermont Auvergne U1071, USC INRA 2018, Clermont Ferrand, France ^aff006
Vyšlo v časopise: The Crohn’s disease-associated Escherichia coli strain LF82 relies on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages. PLoS Pathog 15(11): e32767. doi:10.1371/journal.ppat.1008123
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.ppat.1008123

Souhrn

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.

Klíčová slova:

Antibiotics – Cell cycle and cell division – Death rates – DNA replication – Fluorescence microscopy – Intracellular pathogens – Lysis (medicine) – Macrophages

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