Stern, A M et al., A Novel Protein Protects Bacterial Iron-Dependent Metabolism from Nitric Oxide. Journal of Bacteriology, 2013. 195(20): 4702-4708.
Reactive nitrogen species (RNS), in particular nitric oxide (NO), are toxic to bacteria, and bacteria have mechanisms to allowgrowth despite this stress. Understanding how bacteria interact with NO is essential to understanding bacterial physiology inmany habitats, including pathogenesis; however, many targets of NO and enzymes involved in NO resistance remain uncharacterized.We performed for the first time a metabolomic screen on NO-treated and -untreated bacteria to define broadly the effectsof NO on bacterial physiology, as well as to identify the function of NnrS, a previously uncharacterized enzyme involved indefense against NO. We found many known and novel targets of NO. We also found that iron-sulfur cluster enzymes were preferentiallyinhibited in a strain lacking NnrS due to the formation of iron-NO complexes. We then demonstrated that NnrS isparticularly important for resistance to nitrosative stress under anaerobic conditions. Our data thus reveal the breadth of thetoxic effects of NO on metabolism and identify the function of an important enzyme in alleviating this stress.