Abstract
Nitric oxide (NO ) is a versatile molecular mediator that is generated enzymatically or chemically within the host and exerts broad-spectrum antimicrobial activity. Production of NO by phagocytic cells is augmented in response to inflammation. Sequential production of bactericidal reactive oxygen species and bacteriostatic NO is observed in both macrophages and mice during infection with the enteric bacterial pathogen Salmonella enterica . The reaction of NO with metal centers and thiols inhibits bacterial respiration, DNA replication and specific metabolic pathways including the tricarboxylic acid cycle. NO is predominantly detoxified by the Hmp flavohemoglobin, whose expression is exquisitely responsive to low concentrations of NO . The Gram-positive bacterium Staphylococcus aureus escapes NO inhibition by expressing Hmp in concert with inducible homolactic fermentation, which serves to maintain redox balance during nitrosative stress. This may account for the unique ability of this pathogen to withstand high NO concentrations present in the nose.
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