Endogenous nitric oxide protects bacteria against a wide spectrum of antibiotics.
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.
Gusarov
Ivan
I
Department of Biochemistry, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
Shatalin
Konstantin
K
Starodubtseva
Marina
M
Nudler
Evgeny
E
D000167:Acriflavine / Q000378:metabolism / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000378:metabolism / Q000494:pharmacology*; D000898:Antibiosis; D001408:Bacillus anthracis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D001412:Bacillus subtilis / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D002444:Cefuroxime / Q000494:pharmacology; D009154:Mutation; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress; D011550:Pseudomonas aeruginosa / Q000254:growth & development / Q000378:metabolism; D011710:Pyocyanine / Q000378:metabolism / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012988:Soil Microbiology; D013211:Staphylococcus aureus / Q000187:drug effects / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
D000900:Anti-Bacterial Agents; D017382:Reactive Oxygen Species; D000167:Acriflavine; D009569:Nitric Oxide; D011710:Pyocyanine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase; D002444:Cefuroxime