Two-stage control of an oxidative stress regulon: the Escherichia coli SoxR protein triggers redox-inducible expression of the soxS regulatory gene

Abstract

Escherichia coli responds to the redox stress imposed by superoxide-generating agents such as paraquat by activating the synthesis of as many as 80 polypeptides. Expression of a key group of these inducible proteins is controlled at the transcriptional level by the soxRS locus (the soxRS regulon). A two-stage control system was hypothesized for soxRS, in which an intracellular redox signal would trigger the SoxR protein as a transcriptional activator of the soxS gene and the resulting increased levels of SoxS protein would activate transcription of the various soxRS regulon genes (B. Demple and C.F. Amábile Cuevas, Cell 67:837-839, 1990). We have constructed operon fusions of the E. coli lac genes to the soxS promoter to monitor soxS transcription. Expression from the soxS promoter is strongly inducible by paraquat in a manner strictly dependent on a functional soxR gene. Several other superoxide-generating agents also trigger soxR(+)-dependent soxS expression, and the inductions by paraquat and phenazine methosulfate were dependent on the presence of oxygen. Numerous other oxidative stress agents (H2O2, gamma rays, heat shock, etc.) failed to induce soxS, while aerobic growth of superoxide dismutase-deficient bacteria triggered soxR-dependent soxS expression. These results indicate a specific redox signal for soxS induction. A direct role for SoxR protein in the activation of the soxS gene is indicated by band-shift and DNase I footprinting experiments that demonstrate specific binding of the SoxR protein in cell extracts to the soxS promoter. The mode of SoxR binding to DNA appears to be similar to that of its homolog MerR in that the SoxR footprint spans the -10 to -35 region of the soxS promoter.

Identification and analysis of aarP, a transcriptional activator of the 2'-N-acetyltransferase in Providencia stuartii

“…The extensive amino acid identity of AarP to both MarA and SoxS of E. coli suggested a possible functional similarity as well. In E. coli, the MarA protein serves to activate a set of genes which govern resistance to a variety of antibiotics (8,16), and the SoxS protein activates genes involved in response to oxidative stress (19,28,38). It has also been shown that MarA and SoxS are capable of activating a common set of genes including sodA, nfo, inaA, micF, zwf, and fumC (2, 7, 11, 24, 26, 31a).…”

“…The AarP protein also displayed extensive similarity to the SoxS protein (42% identity), which activates a regulon in response to redox stress (28,38,39). In E. coli, it has been shown that the presence of soxS on a high-copy-number plasmid will result in constitutive expression of some genes in this regulon in the absence of inducing agents such as paraquat (1,39).…”

Paraquat regulation of hmp (flavohemoglobin) gene expression in Escherichia coli K-12 is SoxRS independent but modulated by sigma S

“…The former group includes about 10 proteins whose genes have been firmly identified as components of the soxRS regulon and are necessary for dealing with oxidative stress, including sodA, ompF, fumC, and zwf (2,35,45). The induction of the SoxRS modulon occurs in two steps.…”

“…An unidentified intracellular signal of oxidative stress changes the conformation of the SoxR protein into a transcriptional activator of the soxS gene. The SoxS protein then activates the transcription of genes belonging to the modulon (2,35,46). The SoxRS regulon is activated by redox cycling agents, such as paraquat, plumbagin, menadione, and phenazine methosulfate, all of which generate intracellular superoxide (10,13), and by nitric oxide (35,36).…”

Characterization of secA-sod operon in Borrellia burgdorferi.

“…Elevated levels of O2 -induce the two-component system, SoxRS (Nunoshiba et al, 1992). SoxR, the sensor, becomes activated in the presence of O2 -thereby causing transcription of soxS.…”