Activation by nitric oxide of an oxidative-stress response that defends Escherichia coli against activated macrophages.

• DOI: 10.1073/pnas.90.21.9993
• Publication Date: 2006-05-31T08:34:20Z
• Authors: T Nunoshiba; T deRojas-Walker; J S Wishnok; S R Tannenbaum; B Demple
• Keywords: 0301 basic medicine; Hypoxanthine; Superoxide Dismutase; Macrophages; Mice, Inbred Strains; Gene Expression Regulation, Bacterial; Hydrogen Peroxide; Macrophage Activation; Nitric Oxide; Regulon; Gene Expression Regulation, Enzymologic; 3. Good health; Mice; 03 medical and health sciences; Genes, Bacterial; Superoxides; Enzyme Induction; Hypoxanthines; Operon; Escherichia coli; Animals; Female; Cloning, Molecular

Nitric oxide is a free radical (NO) formed biologically through the oxidation of L-arginine by nitric synthases. NO produced transiently in mammalian cells for intercellular signaling and copious quantities to cause cytostasis cytotoxicity. In latter situation, deliberate cytotoxic product activated macrophages, along with other reactive oxygen species such as hydrogen peroxide (H2O2) superoxide (O2-). Escherichia coli has complex set responses H2O2 O2- that involves approximately 80 inducible proteins; we wondered whether these bacteria might induce analogous defenses against oxide. We show here multigene system controlled redox-sensitive transcriptional regulator SoxR vivo. This induction confers bacterial resistance murine macrophages kinetics parallel production cells. Elimination specific SoxR-regulated genes diminishes macrophages. The required functions include manganese-containing dismutase, endonuclease IV (a DNA-repair enzyme oxidative damage), micF, an antisense outer membrane porin OmpF. These results demonstrate sensor cellular exposure NO, soxRS response may contribute virulence.