Nitrosative Stress: Activation of the Transcription Factor OxyR

Hydrogen peroxide (H2O2) imposes an oxidative stress to Escherichia coli that is manifested by oxidation of glutathione and related redox-sensitive targets. OxyR is a thiol-containing transcriptional activator whose oxidation controls the expression of genes involved in H2O2 detoxification. Here we report that certain S-nitrosothiols (RSNOs) impose what we term a "nitrosative stress" to E. coli, evidenced by lowering of intracellular thiol and the transcriptional activation of OxyR by S-nitrosylation. This cellular and genetic response determines the metabolic fate of RSNOs and thereby contributes to bacterial rescue from stasis. Our studies reveal that signaling by S-nitrosylation can extend to the level of transcription and describe a metabolic pathway that constitutes an adaptation to nitrosative stress.