Jan 27, 2014

A shared alarmone-GTP switch underlies triggered and spontaneous persistence

BioRxiv : the Preprint Server for Biology
David N OlivieriJue Wang

Abstract

Phenotypically-switched, antibiotic-refractory persisters may prevent pathogen eradication. Although how triggered persistence via starvation-induced (p)ppGpp is well characterized, generation of persisters without starvation are poorly understood. Here we visualized the formation of spontaneous persisters in a small fraction of cells from growing wild type bacteria, revealing a striking single cell rapid switch from growth to dormancy. This switch-like entrance is triggered by GTP dropping beneath a threshold due to stochastic production and self-amplification of (p)ppGpp via allosteric enzyme activation. In addition, persisters are induced by lethal and sublethal concentrations of cell wall antibiotics by inducing (p)ppGpp via cell wall stress response. Thus spontaneous, triggered and antibiotic-induced persisters can all stem from a common metabolic switch: GTP depletion by (p)ppGpp induction, and each pathway of persister formation is activated by different (p)ppGpp synthetases. These persistence pathways are likely conserved in pathogens which may be exploited to potentiate antibiotic efficacy.

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Mentioned in this Paper

Vertebrates
T-Lymphocyte
Immunoglobulin Activity
Exons
Genome
Genes
Phylogenetic Analysis
Cell Nucleus
Immunoglobulins
Location

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