Extracytoplasmic function σ factors of the widely distributed group ECF41 contain a fused regulatory domain

Bacteria need signal transducing systems to respond to environmental changes. Next to one- and two-component systems, alternative sigma factors of the extra-cytoplasmic function (ECF) protein family represent the third fundamental mechanism of bacterial signal transduction. A comprehensive classification of these proteins identified more than 40 phylogenetically distinct groups, most of which are not experimentally investigated. Here, we present the characterization of such a group with unique features, termed ECF41. Among analyzed bacterial genomes, ECF41 sigma factors are widely distributed with about 400 proteins from 10 different phyla. They lack obvious anti-sigma factors that typically control activity of other ECF sigma factors, but their structural genes are often predicted to be cotranscribed with carboxymuconolactone decarboxylases, oxidoreductases, or epimerases based on genomic context conservation. We demonstrate for Bacillus licheniformis and Rhodobacter sphaeroides that the corresponding genes are preceded by a highly conserved promoter motif and are the only detectable targets of ECF41-dependent gene regulation. In contrast to other ECF sigma factors, proteins of group ECF41 contain a large C-terminal extension, which is crucial for sigma factor activity. Our data demonstrate that ECF41 sigma factors are regulated by a novel mechanism based on the presence of a fused regulatory domain.