Birth and Resuscitation of (p)ppGpp Induced Antibiotic Tolerant Persister Cells

Svenningsen, Mikkel Skjoldan and Veress, Alexandra and Harms, Alexander and Mitarai, Namiko and Semsey, Szabolcs. (2019) Birth and Resuscitation of (p)ppGpp Induced Antibiotic Tolerant Persister Cells. Scientific Reports, 9 (1). p. 6056.

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Official URL: https://edoc.unibas.ch/71592/

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Transient antibiotic treatment typically eradicates most sensitive bacteria except a few survivors called persisters. The second messenger (p)ppGpp plays a key role in persister formation in Escherichia coli populations but the underlying mechanisms have remained elusive. In this study we induced (p)ppGpp synthesis by modulating tRNA charging and then directly observed the stochastic appearance, antibiotic tolerance, and resuscitation of persister cells using live microscopy. Different physiological parameters of persister cells as well as their regularly growing ancestors and sisters were continuously monitored using fluorescent reporters. Our results confirmed previous findings that high (p)ppGpp levels are critical for persister formation, but the phenomenon remained strikingly stochastic without any correlation between (p)ppGpp levels and antibiotic tolerance on the single-cell level. We could not confirm previous notions that persisters exhibit markedly low concentrations of intracellular ATP or were linked to post-transcriptional effects of (p)ppGpp through the activation of small genetic elements known as toxin-antitoxin (TA) modules. Instead, we suggest that persister cell formation under regular conditions is driven by the transcriptional response to increased (p)ppGpp levels.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Molecular Microbiology (Jenal) > Molecular Microbiology (Harms)
05 Faculty of Science > Departement Biozentrum > Growth & Development > Molecular Microbiology (Jenal) > Molecular Microbiology (Harms)
UniBasel Contributors:Harms, Alexander
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 Nov 2020 16:36
Deposited On:09 Nov 2020 16:36

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