Peroxynitrite reductase activity of bacterial peroxiredoxins

Nitric oxide (NO) is present in soil and air, and is produced by bacteria, animals and plants. Superoxide (O-2(-)) arises in all organisms inhabiting aerobic environments. Thus, many organisms are likely to encounter peroxyni trite (OONO-), a product of NO and O-2(-) that forms at near diffusion-limi ted rates, and rapidly decomposes upon protonation through isomerization to nitrate (NO3-; ref. 1) while generating hydroxyl radical ((OH)-O-.) and ni trogen dioxide radical ((NO2)-N-.) (refs 2, 3), both more reactive than per oxynitrite's precursors. The oxidative, inflammatory, mutagenic and cytotox ic potential (ref. 4) of peroxynitrite contrasts with the antioxidant, anti -inflammatory and tissue-protective properties ascribed to NO itself(5). Th us, the ability of cells to cope with peroxynitrite is central in determini ng the biological consequences of NO production. We considered whether cell s might be equipped with enzymes to detoxify peroxynitrite. Peroxiredoxins have been identified in most genomes sequenced, but their functions are onl y partly understood. Here we show that the peroxiredoxin alkylhydroperoxide reductase subunit C (AhpC) from Salmonella typhimurium catalytically detox ifies peroxynitrite to nitrite fast enough to forestall the oxidation of by stander molecules such as DNA. Results are similar with peroxiredoxins from Mycobacterium tuberculosis and Helicobacter pylori. Thus, peroxynitrite re ductase activity may be widespread among bacterial genera.