Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics

Science. 2009 Sep 11;325(5946):1380-4. doi: 10.1126/science.1175439.

Abstract

Bacterial nitric oxide synthases (bNOS) are present in many Gram-positive species and have been demonstrated to synthesize NO from arginine in vitro and in vivo. However, the physiological role of bNOS remains largely unknown. We show that NO generated by bNOS increases the resistance of bacteria to a broad spectrum of antibiotics, enabling the bacteria to survive and share habitats with antibiotic-producing microorganisms. NO-mediated resistance is achieved through both the chemical modification of toxic compounds and the alleviation of the oxidative stress imposed by many antibiotics. Our results suggest that the inhibition of NOS activity may increase the effectiveness of antimicrobial therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acriflavine / metabolism
  • Acriflavine / pharmacology
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Antibiosis
  • Bacillus anthracis / drug effects
  • Bacillus anthracis / genetics
  • Bacillus anthracis / growth & development
  • Bacillus anthracis / metabolism
  • Bacillus subtilis / drug effects
  • Bacillus subtilis / genetics
  • Bacillus subtilis / growth & development
  • Bacillus subtilis / metabolism
  • Bacteria / drug effects*
  • Bacteria / genetics
  • Bacteria / growth & development
  • Bacteria / metabolism*
  • Cefuroxime / pharmacology
  • Mutation
  • Nitric Oxide / metabolism*
  • Nitric Oxide / pharmacology
  • Nitric Oxide Synthase / genetics
  • Nitric Oxide Synthase / metabolism*
  • Oxidative Stress
  • Pseudomonas aeruginosa / growth & development
  • Pseudomonas aeruginosa / metabolism
  • Pyocyanine / metabolism
  • Pyocyanine / pharmacology
  • Reactive Oxygen Species / metabolism
  • Soil Microbiology
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / genetics
  • Staphylococcus aureus / growth & development
  • Staphylococcus aureus / metabolism
  • Superoxide Dismutase / metabolism

Substances

  • Anti-Bacterial Agents
  • Reactive Oxygen Species
  • Acriflavine
  • Nitric Oxide
  • Pyocyanine
  • Nitric Oxide Synthase
  • Superoxide Dismutase
  • Cefuroxime