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

Sarah A. Sacco, Kristin J. Adolfsen, Mark P. Brynildsen

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

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 (O2), with O2 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 [O2] 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 O2 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 [O2] 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.

Original languageEnglish (US)
Article number1600570
JournalBiotechnology Journal
Volume12
Issue number8
DOIs
StatePublished - Aug 2017

All Science Journal Classification (ASJC) codes

  • Applied Microbiology and Biotechnology
  • Molecular Medicine

Keywords

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

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