title: Bacterial competition and quorum-sensing signalling shape the eco-evolutionary outcomes of modelin vitrophage therapy.
abstract: 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-deficientlasR Pseudomonas aeruginosagenotypes (differing in their ability to signal intraspecifically) to lytic PT7 phage in the presence and absence of two bacterial competitors:Staphylococcus aureusandStenotrophomonas maltophilia-two bacteria commonly associated withP. aeruginosain polymicrobial cystic fibrosis lung infections. Both theP. aeruginosagenotype and the presence of competitors had profound effects on bacteria and phage densities and bacterial resistance evolution. In general, competition reduced theP. aeruginosafrequencies 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-deficientlasRpathogen 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.
authors.affiliation: Silwood Park Campus Imperial College London Ascot Berkshire UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Mumford
authors.affiliation: Silwood Park Campus Imperial College London Ascot Berkshire UK; Department of Biology University of York York UK.
authors.forename: Ville-Petri
authors.initials: VP
authors.lastname: Friman
keywords: coevolution; competition; cost of resistance; host–parasite interactions; phage therapy; polymicrobial infections; quorum‐sensing signalling; resistance