CedA: A General Transcription Factor from E. coli with a Distinct Mechanism of Action

Gene expression in E. coli is controlled by well-established mechanisms that activate or repress transcription. In this study, we identify CedA as an unconventional transcription factor specifically associated with the RNA polymerase (RNAP) Sigma70 holoenzyme. Structural and biochemical analysis of CedA bound to RNAP reveal that it bridges distant domains of Beta and Sigma70 subunits to stabilize an open-promoter complex. We further show that cedA is strongly induced in response to amino acid starvation, oxidative stress, and aminoglycosides. CedA provides a basal level of tolerance to these clinically relevant antibiotics, as well as to rifampicin and peroxide. Finally, we show that CedA modulates transcription of hundreds of bacterial genes, which explains its pleotropic effect on cell physiology and pathogenesis.