Mechanisms of bacterial persistence during stress and antibiotic exposure

Science. 2016 Dec 16;354(6318):aaf4268. doi: 10.1126/science.aaf4268.

Abstract

Bacterial persister cells avoid antibiotic-induced death by entering a physiologically dormant state and are considered a major cause of antibiotic treatment failure and relapsing infections. Such dormant cells form stochastically, but also in response to environmental cues, by various pathways that are usually controlled by the second messenger (p)ppGpp. For example, toxin-antitoxin modules have been shown to play a major role in persister formation in many model systems. More generally, the diversity of molecular mechanisms driving persister formation is increasingly recognized as the cause of physiological heterogeneity that underlies collective multistress and multidrug tolerance of persister subpopulations. In this Review, we summarize the current state of the field and highlight recent findings, with a focus on the molecular basis of persister formation and heterogeneity.

Publication types

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

MeSH terms

  • Adaptation, Physiological / genetics
  • Adaptation, Physiological / physiology*
  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteria / drug effects*
  • Bacteria / metabolism
  • Bacterial Infections / drug therapy
  • Bacterial Infections / microbiology*
  • Bacterial Proteins / metabolism
  • Bacterial Toxins / antagonists & inhibitors
  • Bacterial Toxins / metabolism
  • Biofilms
  • DNA Damage
  • Drug Resistance, Multiple, Bacterial*
  • Guanosine Pentaphosphate / metabolism
  • Proton-Motive Force
  • SOS Response, Genetics
  • Sigma Factor / metabolism
  • Signal Transduction
  • Stochastic Processes
  • Stress, Physiological / genetics
  • Stress, Physiological / physiology*

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Bacterial Toxins
  • Sigma Factor
  • sigma factor KatF protein, Bacteria
  • Guanosine Pentaphosphate