Prion-like characteristics of the bacterial protein Microcin E492

Microcin E492 (Mcc) is a pore-forming bacteriotoxin. Mcc activity is inhibited at the stationary phase by formation of amyloid-like aggregates in the culture. Here we report that, in a similar manner as prions, Mcc naturally exists as two conformers: a β-sheet-rich, protease-resistant, aggregated, inactive form (Mcc^ia), and a soluble, protease-sensitive, active form (Mcc^a). The exogenous addition of culture medium containing Mcc^ia or purified in vitro-generated Mcc^ia into the culture induces the rapid and efficient conversion of Mcc^a into Mcc^ia, which is maintained indefinitely after passaging, changing the bacterial phenotype. Mcc^ia prion-like activity is conformation-dependent and could be reduced by immunodepleting Mcc^ia. Interestingly, an internal region of Mcc shares sequence similarity with the central domain of the prion protein, which is key to the formation of mammalian prions. A synthetic peptide spanning this sequence forms amyloid-like fibrils in vitro and is capable of inducing the conversion of Mcc^a into Mcc^ia in vivo, suggesting that this region corresponds to the prion domain of Mcc. Our findings suggest that Mcc is the first prokaryotic protein with prion properties which harnesses prion-like transmission to regulate protein function, suggesting that propagation of biological information using a prion-based conformational switch is an evolutionary conserved mechanism.