Regulation Of Oxidative Stress In Shewanella Elegans: The Cross-effect Of OxyR And OhrR Regulators In Response

Microorganisms live in environments where they encounter abundant and varied stress-inducing agents, both chemical and physical. To cells in aerobic environments, oxidative stress that caused by reactive oxygen species (ROS) is arguably the most unavoidable stress, because ROS can be generated endogenously, and most is the by-products of normal aerobic physiological metabolism. ROS consist of a variety of chemically reactive molecules, such as free radicals, oxides and peroxides, which is deleterious by damaging DNA, RNA, proteins, and lipids, leading to an increased rate of mutagenesis and cell death. In bacteria, a large number of ROS scavenging enzymes, as well as repair and detoxification systems, are present to restrain intracellular concentrations of ROS in order to prevent the damages beyond unmanageable. Oxidative stress response is a cellular mechanism that maintains the balance between the production of ROS and the ability to readily detect their presence and detoxify them or repair the resulting damages. In bacteria, such response is predominantly mediated by three well-studied transcriptional regulators, SoxRS, OxyR(or PerR) and OhrR, which can directly sense the levels of specific ROS, and upon their oxidation increase expression of genes involved in the detoxification of the substances.Shewanella oneidensis, renowned for its remarkable respiratory abilities, inhabit redox-stratified environments prone to ROS formation. Two major oxidative stress regulators, analogues of OxyR and OhrR, specifically respond to H2O2 and organic peroxides (OP), respectively, are encoded in the genome based on sequence comparison to well-studied models. Presumably, these analogues provide protection from ROS. An understanding of S. oneidensis OxyR has been established recently, which functions as both repressor and activator to mediate H2O2-induced oxidative stress. Here, we report the first study of elucidating molecular mechanisms underlying the S. oneidensis response to OP-induced oxidative stress. We show that S. oneidensis has OhrR, an OP stress regulator with two novel features. The sensing and responding residues of OhrR are not equally important for regulation and the regulator directly controls transcription of the SO1563 gene, in addition to the ohr gene which encodes the major OP scavenging protein. Importantly, we present evidence suggesting that the OxyR and OhrR regulons of S. oneidensis appear to be functionally intertwined as both OxyR and OhrR systems can sense and response to H2O2 and OP agents.