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Futile cycling increases sensitivity toward oxidative stress in Escherichia coli

Paper ID Volume ID Publish Year Pages File Format Full-Text
31508 44807 2015 10 PDF Available
Title
Futile cycling increases sensitivity toward oxidative stress in Escherichia coli
Abstract

•A method for identifying experimentally-tractable futile cycles is presented.•Futile cycling elevates endogenous reactive oxygen species production.•Futile cycling increases bacterial sensitivity to oxidative stress.

Reactive oxygen species (ROS) are toxic molecules utilized by the immune system to combat invading pathogens. Recent evidence suggests that inefficiencies in ATP production or usage can lead to increased endogenous ROS production and sensitivity to oxidative stress in bacteria. With this as inspiration, and knowledge that ATP is required for a number of DNA repair mechanisms, we hypothesized that futile cycling would be an effective way to increase sensitivity to oxidative stress. We developed a mixed integer linear optimization framework to identify experimentally-tractable futile cycles, and confirmed metabolic modeling predictions that futile cycling depresses growth rate, and increases both O2 consumption and ROS production per biomass generated. Further, intracellular ATP was decreased and sensitivity to oxidative stress increased in all actively cycling strains compared to their catalytically inactive controls. This research establishes a fundamental connection between ATP metabolism, endogenous ROS production, and tolerance toward oxidative stress in bacteria.

Keywords
Acs, acetyl-coA synthetase; Pta, phosphate acetyltransferase; Ack, acetate kinase; Pck, phosphoenolpyruvate carboxykinase; Ppc, phosphoenolpyruvate carboxylase; fcacs, cycling engaged by overexpression of acetyl-coA synthetase; fcacs⁎, catalytically inact
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Futile cycling increases sensitivity toward oxidative stress in Escherichia coli
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 29, May 2015, Pages 26–35
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us