The molecular mechanisms and physiological consequences of oxidative stress: lessons from a model bacterium

Excess oxygen can disrupt the growth of most organisms, but the underlying mechanisms of damage have proved difficult to unravel. The model bacterium Escherichia coli represents the best understood organism in terms of the effects of and response to oxidative stress.Superoxide (O2−) and hydrogen peroxide (H2O2) are formed within cells when molecular oxygen (O2) adventitiously acquires electrons from the reduced cofactors of flavoproteins.Both O2− and H2O2 can oxidize the exposed Fe–S clusters of a family of dehydratases. This event destabilizes the clusters, and their consequent disintegration eliminates enzyme activity.O2− and H2O2 also inactivate a variety of non-redox enzymes that use single Fe2+ ions as catalytic cofactors.DNA is damaged when H2O2 reacts with the intracellular pool of unincorporated iron. The iron that is released from oxidized metalloproteins enlarges this pool and accelerates this process.The transcription factor OxyR detects modest increments in intracellular H2O2. It activates several responses that help preserve the activities of Fe–S and mononuclear metalloenzymes.The SoxRS system detects redox-active compounds that are released by plants and some bacteria. These compounds can generate toxic doses of O2−, and the SoxRS system acts primarily to minimize the amounts of these compounds inside the cell.Future studies should aim to determine whether the knowledge gained from studying oxidative stress in the facultative anaerobe E. coli is applicable to other organisms, such as strictly aerobic and microaerophilic bacteria.