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

TitleObg and Membrane Depolarization Are Part of a Microbial Bet-Hedging Strategy that Leads to Antibiotic Tolerance.
Publication TypeJournal Article
Year of Publication2015
AuthorsVerstraeten, N., W. Joris Knapen, C. Ines Kint, V. Liebens, B. Van den Bergh, L. Dewachter, J. Elie Michiels, Q. Fu, C. Claudia David, A. Carolina Fierro, K. Marchal, J. Beirlant, W. Versées, J. Hofkens, M. Jansen, M. Fauvart, and J. Michiels
JournalMol Cell
Volume59
Issue1
Pagination9-21
Date Published2015 Jul 02
ISSN1097-4164
KeywordsAnti-Bacterial Agents, Bacterial Proteins, Bacterial Toxins, Cell Membrane, Drug Resistance, Bacterial, Escherichia coli, Escherichia coli Proteins, GTP-Binding Proteins, Membrane Potentials, Microbial Sensitivity Tests, Protein Structure, Tertiary, Pseudomonas aeruginosa
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.

DOI10.1016/j.molcel.2015.05.011
Alternate JournalMol. Cell
PubMed ID26051177
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