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

• Published in: PLoS pathogens Vol. 15; no. 11; p. e1008123
• Main Authors: Demarre, Gaëlle, Prudent, Victoria, Schenk, Hanna, Rousseau, Emilie, Bringer, Marie-Agnès, Barnich, Nicolas, Tran Van Nhieu, Guy, Rimsky, Sylvie, De Monte, Silvia, Espéli, Olivier
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 14.11.2019; Public Library of Science (PLoS)
• Subjects: Anti-Bacterial Agents - pharmacology; Antibiotics; Bacteria; Bacterial Adhesion; Biology and Life Sciences; Cell Communication; Cell cycle; Cells, Cultured; Crohn Disease - microbiology; Crohn's disease; Drug Resistance, Bacterial; E coli; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Escherichia coli - pathogenicity; Escherichia coli Infections - drug therapy; Escherichia coli Infections - genetics; Escherichia coli Infections - microbiology; Evolutionary biology; Farmers; Funding; Genetic analysis; Genetic research; Genotoxicity; Heterogeneity; Humans; Infections; Intracellular; Life Sciences; Macrophages; Macrophages - drug effects; Macrophages - microbiology; Mathematical models; Medicine and Health Sciences; Metabolism; Microbial drug resistance; Microbiology and Parasitology; Multiplication; Pathogens; Phagolysosomes; Population; Recurrence (Disease); Research and Analysis Methods; Software; SOS Response, Genetics - drug effects; Stringent response; Surgery; Switches; France; Germany; Death rates; Intracellular pathogens; DNA replication; Antibiotics; Macrophages; Lysis (medicine); Cell cycle and cell division; Fluorescence microscopy
• ISSN: 1553-7374; 1553-7366; 1553-7374
• DOI: 10.1371/journal.ppat.1008123

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.