Polyamines reduce oxidative stress in Escherichia coli cells exposed to bactericidal antibiotics

Res Microbiol. 2012 Feb;163(2):83-91. doi: 10.1016/j.resmic.2011.10.009. Epub 2011 Nov 16.

Abstract

Bactericidal antibiotics (fluoroquinolones, aminoglycosides and cephalosporins) at their sublethal concentrations were able to produce hydroxyl radicals, hydrogen peroxide and superoxide anions (ROS) in Escherichia coli cells, which resulted in damage to proteins and DNA. The cells responded to oxidative stress by a 2-3-fold increase in cell polyamines (putrescine, spermidine) produced as a consequence of upregulation of ornithine decarboxylase (ODC). Relief of oxidative stress by cessation of culture aeration or addition of antioxidants substantially diminished or even completely abolished polyamine accumulation observed in response to antibiotics. Alternatively, inhibition of polyamine synthesis resulted in enhancement of oxidative stress in antibiotic-processed cells. When added to antibiotic-inhibited culture, polyamines reduced intracellular ROS production and thereby prevented damage to proteins and DNA. These effects eventually resulted in a substantial increase in cell viability, growth recovery and antibiotic resistance that were more strongly expressed in polyamine-deficient mutants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoglycosides / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Cefotaxime / pharmacology
  • Drug Resistance, Bacterial
  • Escherichia coli / drug effects*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Escherichia coli Proteins / biosynthesis
  • Gene Expression Regulation, Bacterial / drug effects
  • Hydrogen Peroxide / metabolism
  • Microbial Sensitivity Tests
  • Ofloxacin / pharmacology
  • Ornithine Decarboxylase / biosynthesis
  • Ornithine Decarboxylase / metabolism
  • Ornithine Decarboxylase Inhibitors
  • Oxidative Stress / drug effects*
  • Putrescine / biosynthesis*
  • Putrescine / metabolism
  • Spermidine / biosynthesis*
  • Spermidine / metabolism
  • Superoxides / metabolism
  • Trans-Activators / biosynthesis

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Escherichia coli Proteins
  • Ornithine Decarboxylase Inhibitors
  • Trans-Activators
  • Superoxides
  • SoxS protein, E coli
  • Ofloxacin
  • Hydrogen Peroxide
  • Ornithine Decarboxylase
  • Cefotaxime
  • Spermidine
  • Putrescine