(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 Citationer (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.

Originalsprog	Engelsk
Tidsskrift	Cell
Vol/bind	154
Udgave nummer	5
Sider (fra-til)	1140-1150
Antal sider	11
ISSN	0092-8674
DOI	https://doi.org/10.1016/j.cell.2013.07.048
Status	Udgivet - 29 aug. 2013
Udgivet eksternt	Ja

Adgang til dokumentet

10.1016/j.cell.2013.07.048

Citationsformater

@article{fb8f3171ffc74c2b9fcfc7e3340b28a2,

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",

year = "2013",

month = aug,

day = "29",

doi = "10.1016/j.cell.2013.07.048",

language = "English",

volume = "154",

pages = "1140--1150",

journal = "Cell",

issn = "0092-8674",

publisher = "Cell Press",

number = "5",

}

TY - JOUR

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

AU - Maisonneuve, Etienne

AU - Castro-Camargo, Manuela

AU - Gerdes, Kenn

PY - 2013/8/29

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

M3 - Journal article

C2 - 23993101

SN - 0092-8674

VL - 154

SP - 1140

EP - 1150

JO - Cell

JF - Cell

IS - 5

ER -