X(p)ppGpp controls bacterial persistence by stochastic induction of toxin-antitoxin activity

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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 wild-type 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. © 2013 Elsevier Inc.

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Maisonneuve, E., Castro-Camargo, M., & Gerdes, K. (2013). X(p)ppGpp controls bacterial persistence by stochastic induction of toxin-antitoxin activity. Cell, 154(5), 1140. https://doi.org/10.1016/j.cell.2013.07.048

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