The evolution of antibiotic resistance in bacteria is a global concern and the use of bacteriophages alone or in combined therapies is attracting increasing attention as an alternative. Evolutionary theory predicts that the probability of bacterial resistance to both phages and antibiotics will be lower than to either separately, due for example to fitness costs or to trade-offs between phage resistance mechanisms and bacterial growth. In this study, we assess the population impacts of either individual or combined treatments of a bacteriophage and streptomycin on the nosocomial pathogen Pseudomonas aeruginosa. We show that combining phage and antibiotics substantially increases bacterial control compared to either separately, and that there is a specific time delay in antibiotic introduction independent of antibiotic dose, that minimizes both bacterial density and resistance to either antibiotics or phage. These results have implications for optimal combined therapeutic approaches.

Generalist bacterial predators are likely to strongly shape many important ecological and evolutionary features of microbial communities, for example by altering the character and pace of molecular evolution, but investigations of such effects are scarce. Here we report how predator-prey interactions alter the evolution of fitness, genomes and phenotypic diversity in coevolving bacterial communities composed of Myxococcus xanthus as predator and Escherichia coli as prey, relative to single-species controls. We show evidence of reciprocal adaptation and demonstrate accelerated genomic evolution specific to coevolving communities, including the rapid appearance of mutator genotypes. Strong parallel evolution unique to the predator-prey communities occurs in both parties, with predators driving adaptation at two prey traits associated with virulence in bacterial pathogens—mucoidy and the outer-membrane protease OmpT. Our results suggest that generalist predatory bacteria are important determinants of how complex microbial communities and their interaction networks evolve in natural habitats.

Antibiotic resistance is becoming increasingly problematic for the treatment of infectious disease in both humans and livestock. The bacterium Pseudomonas aeruginosa is often found to be resistant to multiple antibiotics and causes high patient mortality in hospitals. Bacteriophages represent a potential option to combat pathogenic bacteria through their application in phage therapy. Here, we capitalize on previous studies showing how evolution may increase phage infection capacity relative to ancestral genotypes. We passaged four different phage isolates (podoviridae, myoviridae) through six serial transfers on the ancestral strain of Pseudomonas aeruginosa PAO1. We first demonstrate that repeated serial passage on ancestral bacteria increases infection capacity of bacteriophage on ancestral hosts and on those evolved for one transfer. This result is confirmed when examining the ability of evolved phage to reduce ancestral host population sizes. Second, through interaction with a single bacteriophage for 24 h, P. aeruginosa can evolve resistance to the ancestor of that bacteriophage; this also provides these evolved bacteria with cross-resistance to the other three bacteriophages. We discuss how the evolutionary training of phages could be employed as effective means of combatting bacterial infections or disinfecting surfaces in hospital settings, with reduced risk of bacterial resistance compared with conventional methods.