A bacterial global regulator forms a prion

Prions are self-propagating protein aggregates that act as protein-based genetic elements in fungi. Although prevalent in eukaryotes, prions have not been identified in bacteria. Here we demonstrate that a bacterial protein, transcription terminator Rho of Clostridium botulinum (Cb-Rho), can form a prion. Specifically, we identify a candidate prion-forming domain (cPrD) in Cb-Rho and show that it confers amyloidogenicity on Cb-Rho and can functionally replace the PrD of a yeast prion-forming protein. Furthermore, we show that its cPrD enables Cb-Rho to access alternative conformations in bacteria, a soluble form that terminates transcription efficiently and an aggregated, self-propagating prion form that is functionally compromised, causing genome-wide changes in the transcriptome. Thus, Cb-Rho functions as a protein-based genetic element in bacteria, suggesting that the emergence of prions predates the evolutionary split between eukaryotes and bacteria. Transcription profiling of cells descended from two blue (prion-containing) colonies and three pale (prion-lacking) colonies reveals genome-wide readthrough of Rho-dependent terminators in cells containing the Rho prion