Colicin Evolution: Lessons from Billions of Years of Bacterial Warfare

Bacteriocins are a diverse group of antimicrobial proteins produced by bacteria. Since bacteriocins are able to kill all known species of bacteria, they are a potential solution to the antibiotic resistance crisis. We used colicins, bacteriocins produced by Escherichia coli, as a model system to understand bacteriocin evolution. We found that colicins that kill via pore-formation and nuclease activity experience different selective pressures. Pore-forming colicins vary greatly in their translocation and receptor-binding domains, which are used to enter target cells. The low fitness cost and high occurrence of receptor mutations in colicin-resistant E. coli explains the large number of receptors used by pore-formers. In contrast, nuclease colicins are highly similar in their translocation and receptor-binding domains but are dissimilar in their killing domain. Nucleases are proteolytically cleaved as part of their cell-entry process, and the site of proteolytic cleavage marks the division between the similar cell-entry domains and the dissimilar killing domain. By understanding how nature selects for colicins, we can make predictions about future evolution, inform decisions about creating bioengineered colicins, and evaluate bacteriocins’ potential as a novel antimicrobial.