ABSTRACT The soxRS response, which protects cells against superoxide toxicity, is triggered by the oxidation of SoxR, a transcription factor. Superoxide excess and NADPH depletion induce the regulon. Unexpectedly, we found that the overproduction of desulfoferrodoxin, a superoxide reductase from sulfate-reducing bacteria, also induced this response. We suggest that desulfoferrodoxin interferes with the reducing pathway that keeps SoxR in its inactive form.