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Inhibition of stationary phase respiration impairs persister formation in E. coli

Mehmet A Orman1, Mark P Brynildsen1

  • 1Department of Chemical and Biological Engineering, Princeton University, Princeton, New Jersy 08544, USA.

Nature Communications
|August 7, 2015
PubMed

Insights

Bacterial persisters, cells tolerant to antibiotics, are reduced when respiration is inhibited during stationary phase. This strategy prevents persister formation and antibiotic tolerance in Escherichia coli.

Area of Science:

  • Microbiology
  • Bacterial Physiology
  • Antibiotic Resistance

Background:

  • Bacterial persisters are phenotypic variants that survive high antibiotic concentrations.
  • Persisters are implicated in recalcitrant biofilm infections, hindering treatment outcomes.
  • Understanding persister formation is crucial for developing effective antimicrobial strategies.

Purpose of the Study:

  • To investigate the role of stationary phase metabolism in the generation of type I persisters in Escherichia coli.
  • To identify metabolic targets for reducing persister formation.

Main Methods:

  • Culturing Escherichia coli in stationary phase.
  • Inhibiting bacterial respiration during stationary phase.
  • Quantifying persister levels and assessing their metabolic activity.

Main Results:

  • Persisters are unlikely to originate from bacteria with low redox activity.
  • Inhibition of respiration during stationary phase reduced persister levels by up to 1,000-fold.
  • Loss of respiratory activity prevented endogenous digestion, enhancing translation and replication upon antibiotic exposure.

Conclusions:

  • Bacterial respiration is a key factor in the formation of type I persisters.
  • Targeting bacterial respiration during stationary phase can significantly reduce persister populations.
  • This offers a potential strategy to improve antibiotic treatment efficacy for persistent infections.

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