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

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  • Etienne Maisonneuve
  • Manuela Castro-Camargo
  • Kenn Gerdes
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.
OriginalsprogEngelsk
TidsskriftCell
Vol/bind154
Udgave nummer5
Sider (fra-til)1140-1150
Antal sider11
ISSN0092-8674
DOI
StatusUdgivet - 2013
Eksternt udgivetJa

ID: 95330976