Leveraging evolutionary trade-offs and phage selection pressure to alter bacterial infections

One possible strategy to combat the antibiotic resistance crisis is a renewed approach to 'phage therapy,' where these administered viruses not only kill the target bacteria, but also predictably select for phage resistance that reduces virulence and/or increases antibiotic sensitivity (evolutionary trade-offs). By utilizing virulence factors as receptor binding sites, the phages exert selection for bacteria to evolve phage resistance by modifying (or losing) the virulence factor, potentially reducing bacterial pathogenicity. We present examples of phages that have evolved to kill target bacteria while selecting for phage resistance that coincides with phenotypic traits that are beneficial to biomedicine. In vitro data on phage-bacteria (co)evolutionary dynamics are often recapitulated in phenotypic, genetic and metagenomics analyses of microbes in longitudinal patient samples before, during and after emergency phage therapy treatments.