The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide
Article first published online: 12 JAN 2011
© 2011 Blackwell Publishing Ltd
Volume 79, Issue 5, pages 1136–1150, March 2011
How to Cite
Gu, M. and Imlay, J. A. (2011), The SoxRS response of Escherichia coli is directly activated by redox-cycling drugs rather than by superoxide. Molecular Microbiology, 79: 1136–1150. doi: 10.1111/j.1365-2958.2010.07520.x
- Issue published online: 21 FEB 2011
- Article first published online: 12 JAN 2011
- Accepted 15 December, 2010.
When Escherichia coli is exposed to redox-cycling drugs, its SoxR transcription factor is activated by oxidation of its [2Fe–2S] cluster. In aerobic cells these drugs generate superoxide, and because superoxide dismutase (SOD) is a member of the SoxRS regulon, superoxide was initially thought to be the activator of SoxR. Its many-gene regulon was therefore believed to comprise a defence against superoxide stress. However, we found that abundant superoxide did not effectively activate SoxR in an SOD- mutant, that overproduced SOD could not suppress activation by redox-cycling drugs, and that redox-cycling drugs were able to activate SoxR in anaerobic cells as long as alternative respiratory acceptors were provided. Thus superoxide is not the signal that SoxR senses. Indeed, redox-cycling drugs directly oxidized the cluster of purified SoxR in vitro, while superoxide did not. Redox-cycling drugs are excreted by both bacteria and plants. Their toxicity does not require superoxide, as they poisoned E. coli under anaerobic conditions, in part by oxidizing dehydratase iron–sulfur clusters. Under these conditions SoxRS induction was protective. Thus it is physiologically appropriate that the SoxR protein directly senses redox-cycling drugs rather than superoxide.