Skip to main content

Discovery and dissection of metabolic oscillations in the microaerobic nitric oxide response network of Escherichia coli

Author(s): Robinson, Jonathan L; Brynildsen, Mark P

To refer to this page use:
Abstract: The virulence of many pathogens depends upon their ability to cope with immune-generated nitric oxide (NO·). In Escherichia coli, the major NO· detoxification systems are Hmp, an NO· dioxygenase (NOD), and NorV, an NO· reductase (NOR). It is well established that Hmp is the dominant system under aerobic conditions, whereas NorV dominates anaerobic conditions; however, the quantitative contributions of these systems under the physiologically relevant microaerobic regime remain ill defined. Here, we investigated NO· detoxification in environments ranging from 0 to 50 μM O2, and discovered a regime in which E. coli NO· defenses were severely compromised, as well as conditions that exhibited oscillations in the concentration of NO·. Using an integrated computational and experimental approach, E. coli NO· detoxification was found to be extremely impaired at low O2 due to a combination of its inhibitory effects on NorV, Hmp, and translational activities, whereas oscillations were found to result from a kinetic competition for O2 between Hmp and respiratory cytochromes. Because at least 777 different bacterial species contain the genetic requirements of this stress response oscillator, we hypothesize that such oscillatory behavior could be a widespread phenomenon. In support of this hypothesis, Pseudomonas aeruginosa, whose respiratory and NO· response networks differ considerably from those of E. coli, was found to exhibit analogous oscillations in low O2 environments. This work provides insight into how bacterial NO· defenses function under the low O2 conditions that are likely to be encountered within host environments.
Publication Date: 22-Mar-2016
Electronic Publication Date: 7-Mar-2016
Citation: Robinson, Jonathan L, Brynildsen, Mark P. (2016). Discovery and dissection of metabolic oscillations in the microaerobic nitric oxide response network of Escherichia coli. Proceedings of the National Academy of Sciences, 113 (12), E1757 - E1766. doi:10.1073/pnas.1521354113
DOI: doi:10.1073/pnas.1521354113
ISSN: 0027-8424
EISSN: 1091-6490
Pages: E1757 - E1766
Type of Material: Journal Article
Journal/Proceeding Title: Proceedings of the National Academy of Sciences
Version: Final published version. Article is made available in OAR by the publisher's permission or policy.

Items in OAR@Princeton are protected by copyright, with all rights reserved, unless otherwise indicated.