The general stress response in Alphaproteobacteria

• The alphaproteobacterial general stress response (GSR) is crucial for Alphaproteobacteria to thrive in natural environments.
• The partner switch controlling the GSR functions via sigma factor mimicry.
• Complex two-component signaling systems control the GSR.

The general stress response (GSR) is a widely conserved response that allows bacteria to cope with a multitude of stressful conditions. In the past years the PhyR–NepR–σEcfG cascade was identified as the core pathway regulating the GSR in Alphaproteobacteria, in which it also plays an important role in bacteria–host interactions. The regulatory system is composed of the extracytoplasmic function sigma factor σEcfG, its anti-sigma factor NepR (for negative regulator of the PhyR response), and the anti-sigma factor antagonist PhyR (phyllosphere regulator). The three proteins function via a partner-switching mechanism that is triggered by PhyR phosphorylation, termed ‘sigma factor mimicry’. This review will cover core features of the pathway, its physiological role, and summarize recent advances towards understanding of the partner-switching mechanism and of the two-component signaling pathways controlling the GSR.