An integrated network analysis identifies how ArcAB enables metabolic oscillations in the nitric oxide detoxification network of Escherichia coli.

<p>The virulences of many pathogens depend on their abilities to detoxify the immune antimicrobial nitric oxide (NO•). The functions of bacterial NO• detoxification machinery depend on oxygen (O ), with O inhibiting some enzymes, whereas others use it as a substrate. Previously, Escherichia coli NO• detoxification was found to be highly attenuated under microaerobic conditions and metabolic oscillations were observed. The oscillations in [NO•] and [O ] were found to result from the inhibitory action of NO• on aerobic respiration, the catalytic inactivation of NO• by Hmp (an NO• dioxygenase), and an imbalanced competition for O between Hmp and cytochrome terminal oxidase activity. Here the authors investigated the role of the ArcAB two component system (TCS) in microaerobic NO• detoxification. The authors observed that wild-type, ΔarcA, and ΔarcB had comparable initial NO• clearance times; however, the mutant cultures failed to exhibit [NO•] and [O ] oscillations. Using an approach that employed experimentation and computational modeling, the authors found that the loss of oscillations in ΔarcA was due to insufficient induction of cytochrome bd-I expression. Collectively, these results establish ArcAB as a TCS that influences NO• detoxification in E. coli within the physiologically-relevant microaerobic regime.</p>