Multiple σ^EcfG and NepR Proteins Are Involved in the General Stress Response in <i>Methylobacterium extorquens</i>

<div><p>In Alphaproteobacteria, the general stress response (GSR) is controlled by a conserved partner switch composed of the sigma factor σ^EcfG, its anti-sigma factor NepR and the anti-sigma factor antagonist PhyR. Many species possess paralogues of one or several components of the system, but their roles remain largely elusive. Among Alphaproteobacteria that have been genome-sequenced so far, the genus <i>Methylobacterium</i> possesses the largest number of σ^EcfG proteins. Here, we analyzed the six σ^EcfG paralogues of <i>Methylobacterium extorquens</i> AM1. We show that these sigma factors are not truly redundant, but instead exhibit major and minor contributions to stress resistance and GSR target gene expression. We identify distinct levels of regulation for the different sigma factors, as well as two NepR paralogues that interact with PhyR. Our results suggest that in <i>M</i>. <i>extorquens</i> AM1, <i>ecfG</i> and <i>nepR</i> paralogues have diverged in order to assume new roles that might allow integration of positive and negative feedback loops in the regulatory system. Comparison of the core elements of the GSR regulatory network in <i>Methylobacterium</i> species provides evidence for high plasticity and rapid evolution of the GSR core network in this genus.</p>