Coordination of frontline defense mechanisms under severe oxidative stress

Abstract

Complexity of cellular response to oxidative stress (OS) stems from its wide-ranging damage to nucleic acids, proteins, carbohydrates, and lipids. We have constructed a systems model of OS response (OSR) for Halobacterium salinarum NRC-1 in an attempt to understand the architecture of its regulatory network that coordinates this complex response. This has revealed a multi-tiered OS-management program to transcriptionally coordinate three peroxidase/catalase enzymes, two superoxide dismutases, production of rhodopsins, carotenoids and gas vesicles, metal trafficking, and various other aspects of metabolism. Through experimental validation of interactions within the OSR regulatory network, we show that despite their inability to directly sense reactive oxygen species, general transcription factors have an important function in coordinating this response. Remarkably, a significant fraction of this OSR was accurately recapitulated by a model that was earlier constructed from cellular responses to diverse environmental perturbations-this constitutes the general stress response component. Notwithstanding this observation, comparison of the two models has identified the coordination of frontline defense and repair systems by regulatory mechanisms that are triggered uniquely by severe OS and not by other environmental stressors, including sub-inhibitory levels of redox-active metals, extreme changes in oxygen tension, and a sub-lethal dose of c rays.

A Major Role for Nonenzymatic Antioxidant Processes in the Radioresistance of Halobacterium salinarum

“…The cellular effects of oxidative stress from exposure to chemical oxidants and to IR were determined for H. salinarum cells exposed to H 2 O 2 , paraquat (an O 2 ⅐ Ϫ generator), and 60 Co gamma radiation. Oxidative damage to DNA and proteins was measured at doses that yielded 80% survival of the cells (32,64). Hydrogen peroxide and IR were applied directly to H. salinarum cells, whereas O 2 ⅐ Ϫ radicals were produced indirectly via exposure to paraquat (25).…”

“…Cultures were grown at 37°C for E. coli and P. putida and at 42°C for H. salinarum, with shaking at 220 rpm in a Gyromax 737 shaker (Amerex Instruments, Lafayette, CA). ROS detoxification mutants with ⌬sod1/2, ⌬perA, ⌬msrA, ⌬VNG0018H, and ⌬VNG0798H mutations have been previously described (32).…”

Protection from Oxidative Stress Relies Mainly on Derepression of OxyR-Dependent KatB and Dps in Shewanella oneidensis

“…OxyR and SoxRS, two main transcriptional systems that respond to oxidative stress in bacteria, are well understood from extensive studies of E. coli (2,(4)(5)(6)(7). The OxyR system is activated in response to hydrogen peroxide (H 2 O 2 ), whereas the SoxRS system is activated in the presence of the superoxide anion.…”

Characterization of a Mycobacterium tuberculosis Nanocompartment and Its Potential Cargo Proteins

“…These observations suggest that Enc proteins compartmentalize DyP or ferritin-like proteins via their C-terminal tails. Notably, both DyPs and ferritin proteins possess antioxidant properties (7,8).…”