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

Mol Cell. 2015 Jul 2;59(1):9-21. doi: 10.1016/j.molcel.2015.05.011. Epub 2015 Jun 4.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Toxins / biosynthesis*
  • Bacterial Toxins / genetics
  • Cell Membrane / physiology
  • Drug Resistance, Bacterial / physiology*
  • Escherichia coli / genetics*
  • Escherichia coli Proteins / biosynthesis*
  • Escherichia coli Proteins / genetics
  • GTP-Binding Proteins / genetics*
  • Membrane Potentials / genetics
  • Microbial Sensitivity Tests
  • Protein Structure, Tertiary / genetics
  • Pseudomonas aeruginosa / genetics*


  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacterial Toxins
  • Escherichia coli Proteins
  • HokB protein, E coli
  • Obg GTP-binding protein, Bacteria
  • GTP-Binding Proteins

Associated data

  • GEO/GSE62918