Molecular mechanisms underlying bacterial persisters

Cell. 2014 Apr 24;157(3):539-48. doi: 10.1016/j.cell.2014.02.050.


All bacteria form persisters, cells that are multidrug tolerant and therefore able to survive antibiotic treatment. Due to the low frequencies of persisters in growing bacterial cultures and the complex underlying molecular mechanisms, the phenomenon has been challenging to study. However, recent technological advances in microfluidics and reporter genes have improved this scenario. Here, we summarize recent progress in the field, revealing the ubiquitous bacterial stress alarmone ppGpp as an emerging central regulator of multidrug tolerance and persistence, both in stochastically and environmentally induced persistence. In several different organisms, toxin-antitoxin modules function as effectors of ppGpp-induced persistence.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Bacteria / drug effects*
  • Bacteria / metabolism
  • Bacterial Physiological Phenomena
  • Drug Resistance, Multiple, Bacterial*
  • Escherichia coli / drug effects
  • Escherichia coli Proteins / genetics
  • Escherichia coli Proteins / metabolism
  • Fungi / drug effects
  • Guanosine Tetraphosphate / metabolism*
  • Signal Transduction


  • Escherichia coli Proteins
  • hipA protein, E coli
  • Guanosine Tetraphosphate