Peroxide-Sensing Transcriptional Regulators in Bacteria

Abstract

© 2016 John Wiley & Sons, Inc. All rights reserved. Exposure to reactive oxygen species (ROS) is a fact of life for aerobic organisms as well as anaerobes that experience transient exposure to oxygen. Aerobic bacteria produce them as a byproduct of normal metabolic activity due to the aberrant transfer of electrons from redox enzyme cofactors to O2. Significant exposure can also originate from external sources like host immune responses or as a secondary effect resulting from other types of stress, such as high osmolarity or antibiotic exposure. ROS, including O2 •Δ, H2O2, and organic peroxides, have the potential to damage nearly all cellular constituents, and their levels must therefore be controlled. Bacteria have evolved oxidative stress defense systems that can function constitutively to keep ROS levels within safe limits during normal growth and that can be upregulated during periods of high exposure to consume ROS and repair and prevent further damage. This inducible response is mediated by regulators that can sense the levels of ROS and activate or de-repress the appropriate target genes. These regulators can also control the expression of genes involved in biological processes like biofilm formation or evasion of host immune responses. This review focuses on three well-studied peroxide-sensing regulators: OxyR and PerR that primarily sense H2O2, and OhrR, which senses organic peroxides and NaOCl. OxyR and OhrR sense peroxides via the oxidation of a sensing cystein residue, while PerR utilizes the ferrous iron-catalyzed oxidation of histidine residues. In all cases, oxidation of the protein changes the DNA-binding properties of the regulator.