Persisters and beyond: mechanisms of phenotypic drug resistance and drug tolerance in bacteria

Crit Rev Biochem Mol Biol. Mar-Apr 2014;49(2):91-101. doi: 10.3109/10409238.2013.869543. Epub 2013 Dec 13.


One of the challenges in clinical infectious diseases is the problem of chronic infections, which can require long durations of antibiotic treatment and often recur. An emerging explanation for the refractoriness of some infections to treatment is the existence of subpopulations of drug tolerant cells. While typically discussed as "persister" cells, it is becoming increasingly clear that there is significant heterogeneity in drug responses within a bacterial population and that multiple mechanisms underlie the emergence of drug tolerant and drug-resistant subpopulations. Many of these parallel mechanisms have been shown to affect drug susceptibility at the level of a whole population. Here we review mechanisms of phenotypic drug tolerance and resistance in bacteria with the goal of providing a framework for understanding the similarities and differences in these cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / cytology
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / growth & development*
  • Bacterial Infections / drug therapy*
  • Bacterial Infections / microbiology*
  • Bacterial Physiological Phenomena / drug effects
  • Biofilms / drug effects
  • Biofilms / growth & development
  • Drug Resistance, Bacterial*
  • Humans


  • Anti-Bacterial Agents