(p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity

Etienne Maisonneuve; Manuela Castro-Camargo; Kenn Gerdes

doi:10.1016/j.cell.2013.07.048

(p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity

Etienne Maisonneuve, Manuela Castro-Camargo, Kenn Gerdes

355 Citations (Scopus)

Abstract

Persistence refers to the phenomenon in which isogenic populations of antibiotic-sensitive bacteria produce rare cells that transiently become multidrug tolerant. Whether slow growth in a rare subset of cells underlies the persistence phenotype has not be examined in wild-type bacteria. Here, we show that an exponentially growing population of wildtype Escherichia coli cells produces rare cells that stochastically switch into slow growth, that the slow-growing cells are multidrug tolerant, and that they are able to resuscitate. The persistence phenotype depends hierarchically on the signaling nucleotide (p)ppGpp, Lon protease, inorganic polyphosphate, and toxin-antitoxins. We show that the level of (p)ppGpp varies stochastically in a population of exponentially growing cells and that the high (p)ppGpp level in rare cells induces slow growth and persistence. (p)ppGpp triggers slow growth by activating toxin-antitoxin loci through a regulatory cascade depending on inorganic polyphosphate and Lon protease.

Original language	English
Journal	Cell
Volume	154
Issue number	5
Pages (from-to)	1140-1150
Number of pages	11
ISSN	0092-8674
DOIs	https://doi.org/10.1016/j.cell.2013.07.048
Publication status	Published - 29 Aug 2013
Externally published	Yes

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10.1016/j.cell.2013.07.048

Cite this

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title = "(p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity",

abstract = "Persistence refers to the phenomenon in which isogenic populations of antibiotic-sensitive bacteria produce rare cells that transiently become multidrug tolerant. Whether slow growth in a rare subset of cells underlies the persistence phenotype has not be examined in wild-type bacteria. Here, we show that an exponentially growing population of wildtype Escherichia coli cells produces rare cells that stochastically switch into slow growth, that the slow-growing cells are multidrug tolerant, and that they are able to resuscitate. The persistence phenotype depends hierarchically on the signaling nucleotide (p)ppGpp, Lon protease, inorganic polyphosphate, and toxin-antitoxins. We show that the level of (p)ppGpp varies stochastically in a population of exponentially growing cells and that the high (p)ppGpp level in rare cells induces slow growth and persistence. (p)ppGpp triggers slow growth by activating toxin-antitoxin loci through a regulatory cascade depending on inorganic polyphosphate and Lon protease.",

author = "Etienne Maisonneuve and Manuela Castro-Camargo and Kenn Gerdes",

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T1 - (p)ppGpp Controls Bacterial Persistence by Stochastic Induction of Toxin-Antitoxin Activity

AU - Maisonneuve, Etienne

AU - Castro-Camargo, Manuela

AU - Gerdes, Kenn

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Y1 - 2013/8/29

N2 - Persistence refers to the phenomenon in which isogenic populations of antibiotic-sensitive bacteria produce rare cells that transiently become multidrug tolerant. Whether slow growth in a rare subset of cells underlies the persistence phenotype has not be examined in wild-type bacteria. Here, we show that an exponentially growing population of wildtype Escherichia coli cells produces rare cells that stochastically switch into slow growth, that the slow-growing cells are multidrug tolerant, and that they are able to resuscitate. The persistence phenotype depends hierarchically on the signaling nucleotide (p)ppGpp, Lon protease, inorganic polyphosphate, and toxin-antitoxins. We show that the level of (p)ppGpp varies stochastically in a population of exponentially growing cells and that the high (p)ppGpp level in rare cells induces slow growth and persistence. (p)ppGpp triggers slow growth by activating toxin-antitoxin loci through a regulatory cascade depending on inorganic polyphosphate and Lon protease.

AB - Persistence refers to the phenomenon in which isogenic populations of antibiotic-sensitive bacteria produce rare cells that transiently become multidrug tolerant. Whether slow growth in a rare subset of cells underlies the persistence phenotype has not be examined in wild-type bacteria. Here, we show that an exponentially growing population of wildtype Escherichia coli cells produces rare cells that stochastically switch into slow growth, that the slow-growing cells are multidrug tolerant, and that they are able to resuscitate. The persistence phenotype depends hierarchically on the signaling nucleotide (p)ppGpp, Lon protease, inorganic polyphosphate, and toxin-antitoxins. We show that the level of (p)ppGpp varies stochastically in a population of exponentially growing cells and that the high (p)ppGpp level in rare cells induces slow growth and persistence. (p)ppGpp triggers slow growth by activating toxin-antitoxin loci through a regulatory cascade depending on inorganic polyphosphate and Lon protease.

U2 - 10.1016/j.cell.2013.07.048

DO - 10.1016/j.cell.2013.07.048

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