Reactive nitrogen intermediates and antimicrobial activity: Role of nitrite

Abstract

The reactive nitrogen intermediate (RNI) nitric oxide (NO ⋅ is formed from l-arginine by an NO ⋅ synthase and, following secondary reactions yielding additional toxic intermediates, nitrite (NO 12 −) and nitrate formed. Nitrite, however, also has toxic properties. At acid pH, nitrous acid (HNO 2) is bactericidal to Escherichia coli, in association with the loss of HNO 2/NO 2 − and the uptake of oxygen, an effect which is increased by H 2O 2. Under conditions in which HNO 2/NO 2 − ± H 2O 2 were ineffective, the further addition of peroxidase (myeloperoxidase [MPO], eosinophil peroxidase, lactoperoxidase) or catalase resulted in bactericidal activity and the disappearance of HNO 2/No 2 − also inhibited the bactericidal activity of MPO by the formation of a complex with MPO with a shift in the absorption spectrum, and by reaction with hypochlorous acid (HOCl) (the product of the chloride-supplemented MPO-H 2O 2 system), with loss of the bactericidal activity of HOCl and the disappearance of both HOCl and HNO 2/NO 2 − from the reaction mixture. Thus, HNO 2/NO 2 −, ra being solely an end product of RNI formation, may influence antimicroboal activity either by acting alone, with H 2O 2, or with H 2O 2 and peroxidase as a source of toxic agents, or by inhibiting the peroxidase-mediated antimicrobial systems.