Obg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance

Natalie Verstraeten, Wouter Joris Knapen, Cyrielle Ines Kint, Veerle Liebens, Bram Van den Bergh, Liselot Dewachter, Joran Elie Michiels, Qiang Fu, Charlotte Claudia David, Ana Carolina Fierro, Kathleen Marchal, Jan Beirlant, Wim Versées, Johan Hofkens, Maarten Jansen, Maarten Fauvart, Jan Michiels

Research output: Contribution to journalArticlepeer-review

214 Citations (Scopus)

Abstract

Within bacterial populations, a small fraction of persister cells is transiently capable of surviving exposure to lethal doses of antibiotics. As a bet-hedging strategy, persistence levels are determined both by stochastic induction and by environmental stimuli called responsive diversification. Little is known about the mechanisms that link the low frequency of persisters to environmental signals. Our results support a central role for the conserved GTPase Obg in determining persistence in Escherichia coli in response to nutrient starvation. Obg-mediated persistence requires the stringent response alarmone (p)ppGpp and proceeds through transcriptional control of the hokB-sokB type I toxin-antitoxin module. In individual cells, increased Obg levels induce HokB expression, which in turn results in a collapse of the membrane potential, leading to dormancy. Obg also controls persistence in Pseudomonas aeruginosa and thus constitutes a conserved regulator of antibiotic tolerance. Combined, our findings signify an important step toward unraveling shared genetic mechanisms underlying persistence.

Original languageEnglish
Pages (from-to)9-21
Number of pages13
JournalMol. Cell
Volume59
Issue number1
DOIs
Publication statusPublished - 2 Jul 2015

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