Extracytoplasmic function (ECF) sigma factor σ(F) is involved in Caulobacter crescentus response to heavy metal stress

BACKGROUND: The α-proteobacterium Caulobacter crescentus inhabits low-nutrient environments and can tolerate certain levels of heavy metals in these sites. It has been reported that C. crescentus responds to exposure to various heavy metals by altering the expression of a large number of genes. RESULTS: In this work, we show that the ECF sigma factor σ(F) is one of the regulatory proteins involved in the control of the transcriptional response to chromium and cadmium. Microarray experiments indicate that σ(F) controls eight genes during chromium stress, most of which were previously described as induced by heavy metals. Surprisingly, σ(F) itself is not strongly auto-regulated under metal stress conditions. Interestingly, σ(F)-dependent genes are not induced in the presence of agents that generate reactive oxygen species. Promoter analyses revealed that a conserved σ(F)-dependent sequence is located upstream of all genes of the σ(F) regulon. In addition, we show that the second gene in the sigF operon acts as a negative regulator of σ(F) function, and the encoded protein has been named NrsF (Negative regulator of sigma F). Substitution of two conserved cysteine residues (C131 and C181) in NrsF affects its ability to maintain the expression of σ(F)-dependent genes at basal levels. Furthermore, we show that σ(F) is released into the cytoplasm during chromium stress and in cells carrying point mutations in both conserved cysteines of the protein NrsF. CONCLUSION: A possible mechanism for induction of the σ(F)-dependent genes by chromium and cadmium is the inactivation of the putative anti-sigma factor NrsF, leading to the release of σ(F) to bind RNA polymerase core and drive transcription of its regulon.