Expansion and re-classification of the extracytoplasmic function (ECF) σ factor family

Extracytoplasmic function sigma factors (ECFs) represent one of the major bacterial signal transduction mechanisms in terms of abundance, diversity and importance, particularly in mediating stress responses. Here, we performed a comprehensive phylogenetic analysis of this protein family by scrutinizing all proteins in the NCBI database. As a result, we identified an average of similar to 10 ECFs per bacterial genome and 157 phylogenetic ECF groups that feature a conserved genetic neighborhood and a similar regulation mechanism. Our analysis expands previous classification efforts similar to 50-fold, enriches many original ECF groups with previously unclassified proteins and identifies 22 entirely new ECF groups. The ECF groups are hierarchically related to each other and are further composed of subgroups with closely related sequences. This two-tiered classification allows for the accurate prediction of common promoter motifs and the inference of putative regulatory mechanisms across subgroups composing an ECF group. This comprehensive, high-resolution description of the phylogenetic distribution of the ECF family, together with the massive expansion of classified ECF sequences and an openly accessible data repository called 'ECF Hub' (https://www.computational , bio.uni-giessen.de/ecfhub), will serve as a powerful hypothesis-generator to guide future research in the field.

Automated summary

Extracytoplasmic function sigma factors (ECFs) play a major role in bacterial signal transduction mechanisms, with our comprehensive phylogenetic analysis identifying numerous new ECF groups and expanding classification efforts. This detailed description of the phylogenetic distribution of the ECF family will serve as a powerful tool for guiding future research in the field.