The Crohn’s disease-associated Escherichia coli strain LF82 rely on SOS and stringent responses to survive, multiply and tolerate antibiotics within macrophages
Autor: | Guy Tran Van Nhieu, Emilie Rousseau, Victoria Prudent, Nicolas Barnich, Hanna Schenk, Gaëlle Demarre, Olivier Espéli, Silvia De Monte, Marie-Agnès Bringer, Sylvie Rimsky |
---|---|
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0303 health sciences
030306 microbiology medicine.drug_class Stringent response Antibiotics Biology Cell cycle medicine.disease_cause biology.organism_classification Microbiology 03 medical and health sciences Pathovar medicine Macrophage Escherichia coli Intracellular Bacteria 030304 developmental biology |
DOI: | 10.1101/551226 |
Popis: | 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. |
Databáze: | OpenAIRE |
Externí odkaz: |