Sensing and protecting against superoxide stress in Escherichia coli--how many ways are there to trigger soxRS response?

Abstract

Reactive oxygen species (ROS) are produced as an inescapable consequence of aerobic life. Their levels are kept low enough to be harmless by specific enzymes, such as superoxide dismutase, which eliminate them. Expression of these defence enzymes is modulated depending on the environmental oxidative threat. This basic protection, however, is not sufficient to protect against sudden large increases in ROS production. To cope with oxidative stress, rapid global responses are induced that enable bacteria to survive the stress period by multiple means: elimination of ROS, repair of oxidative damage, bypass of damaged functions and induction of adapted metabolism. The soxRS response, which protects against superoxide (O2.-)-generating agents and nitric oxide (.NO), is triggered by activation of a sensor molecule, SoxR, containing two essential [2Fe-2S] clusters. The soxRS regulon is induced in a two-stage process. Upon activation, SoxR induces soxS expression and SoxS, in turn, activates transcription of genes of the regulon. The mechanism of signalling has been under debate for years. Evidence for several pathways of SoxR activation, mediated by the modifications of [2Fe-2S] centres, has emerged from recent data. The direct oxidation of [2Fe-2S] centres, any event that may interfere with the pathway maintaining SoxR in a reduced inactive form, and direct nitrosylation by .NO can trigger SoxR activation. The multiple possibilities for SoxR activation, along with signal amplification via the two-stage process, constitute a unique, and particularly sensitive, system enabling cells to induce rapidly a protective response to a broad range of environmental changes indicative of possible oxidative stress.