Pyocyanin produced by Pseudomonas aeruginosa Creates Legacy Effects That Boost Antibiotic Resistance Evolution in Enterococci

Polymicrobial infections are small communities of multiple interacting bacterial species. Interactions among constituent species may modify the growth of community members in the presence of antibiotics, for example via degradation of the antibiotic or induction of specific resistance mechanisms. However, for most polymicrobial infections the nature of such interactions is opaque, while they may affect both treatment efficacy and the evolution of antibiotic resistance. Here, we describe that past interaction of enterococci with Pseudomonas aeruginosa creates legacy effects that substantially alter their antibiotic tolerance and resistance evolution. Specifically, we find that the temporary exposure to pyocyanin, a secondary metabolite produced by P. aeruginosa , increases the efflux in enterococci. These tolerance legacy effects promote the evolution of antibiotic resistance of enterococci. This work shows that transient interactions in polymicrobial communities can alter the evolutionary fate of community members.