Bacterial competition and quorum-sensing signalling shapes the eco-evolutionary outcomes of model in vitro phage therapy

The rapid rise of antibiotic resistance has renewed interest in phage therapy - the use of bacteria-specific viruses (phages) to treat bacterial infections. Even though phages are often pathogen-specific, little is known about the efficiency and eco-evolutionary outcomes of phage therapy in polymicrobial infections. We studied this experimentally by exposing both quorum-sensing (QS) signalling PAO1 and QS-deficient lasR Pseudomonas aeruginosa genotypes (differing in their ability to signal intraspecifically) to lytic PT7 phage in the presence and absence of two bacterial competitors: Staphylococcus aureus and Stenotrophomonas maltophilia-two bacteria commonly associated with P. aeruginosa in polymicrobial cystic fibrosis lung infections. Both the P. aeruginosa genotype and the presence of competitors had profound effects on bacteria and phage densities and bacterial resistance evolution. In general, competition reduced the P. aeruginosa frequencies leading to a lower rate of resistance evolution. This effect was clearer with QS signalling PAO1 strain due to lower bacteria and phage densities and relatively larger pleiotropic growth cost imposed by both phages and competitors. Unexpectedly, phage selection decreased the total bacterial densities in the QS-deficient lasR pathogen communities, while an increase was observed in the QS signalling PAO1 pathogen communities. Together these results suggest that bacterial competition can shape the eco-evolutionary outcomes of phage therapy.