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

作者：Sacco Sarah A; Adolfsen Kristin J; Brynildsen Mark P^*

来源：Biotechnology Journal, 2017, 12(8): 1600570.

DOI：10.1002/biot.201600570

• cydAB
• Hmp
• Microaerobic
• Nitric oxide dioxygenase
• Two component system

The virulences of many pathogens depend on their abilities to detoxify the immune antimicrobial nitric oxide (NO center dot). The functions of bacterial NO center dot detoxification machinery depend on oxygen (O-2), with O-2 inhibiting some enzymes, whereas others use it as a substrate. Previously, Escherichia coli NO center dot detoxification was found to be highly attenuated under microaerobic conditions and metabolic oscillations were observed. The oscillations in [NO center dot] and [O-2] were found to result from the inhibitory action of NO center dot on aerobic respiration, the catalytic inactivation of NO center dot by Hmp (an NO center dot dioxygenase), and an imbalanced competition for O-2 between Hmp and cytochrome terminal oxidase activity. Here the authors investigated the role of the ArcAB two component system (TCS) in microaerobic NO center dot detoxification. The authors observed that wild-type, arcA, and arcB had comparable initial NO center dot clearance times; however, the mutant cultures failed to exhibit [NO center dot] and [O-2] oscillations. Using an approach that employed experimentation and computational modeling, the authors found that the loss of oscillations in arcA was due to insufficient induction of cytochrome bd-I expression. Collectively, these results establish ArcAB as a TCS that influences NO center dot detoxification in E. coli within the physiologically-relevant microaerobic regime.

• 出版日期2017-8