An integrated regulatory network including two positive feedback loops to modulate the activity of σE in mycobacteria.

σE, one of the best characterized mycobacterial extracytoplasmic function sigma factors, is involved in virulence, surface stress response and modulation of the inflammatory response during infection. The regulation of its activity is very complex and involves transcriptional, translational and post-translational control. Post-translational regulation is controlled by RseA, an anti-σ factor belonging to the zinc-associated anti-σ factor family. In this issue of Molecular Microbiology, Barik et al. demonstrate that RseA is a redox-sensing protein that is able to bind σE only in reducing environment. Importantly, they describe a novel positive feedback loop responsible for σE release and activation following surface stress, due to ClpC1P2-dependent proteolytic degradation of RseA, depending on its phosphorylation by the eukaryotic-like Ser/Thr protein kinase PknB. [ABSTRACT FROM AUTHOR]