Outer membrane changes enable evolutionary escape from bacterial predation

To combat antimicrobial resistant pathogens, natural predatory bacteria, like Bdellovibrio bacteriovorus , represent potential alternatives. B. bacteriovorus could be particularly potent as it kills a broad range of human bacterial pathogens, however, it remains unclear whether prey can evolve genetically-determined resistance against predation. Here, we show that the model bacterium Escherichia coli K-12 consistently evolves resistance against B. bacteriovorus during experimental evolution. Selection for resistance scaled positively with predation pressure and was widespread after two cycles of predator exposure. Like antibiotics, predation resistance was costly, manifesting in a trade-off between predation resistance and fitness in the absence of predators. Genetic analysis identified changes in outer membrane porin OmpF as common resistance mechanism, while a mutation in cell envelope lipopolysaccharide-modifying enzyme WaaF was rarer but also conferred predation resistance. Our study uncovers evolutionary and mechanistic aspects of prey escape from predation, generating important knowledge on predator-prey interactions and to advance sustainable treatments.