Loss-of-Function Mutations in epaR Confer Resistance to ϕNPV1 Infection in Enterococcus faecalis OG1RF

is a Gram-positive opportunistic pathogen that inhabits the human gastrointestinal tract. Because of the high frequency of antibiotic resistance among clinical isolates, interest in using phage to treat enterococcal infections and to decolonize high-risk patients for antibiotic-resistant is rising. Bacteria can evolve phage resistance, but there is little published information on these mechanisms in In this report, we identified genetic determinants of resistance to phage NPV1 (ϕNPV1). We found that loss-of-function mutations in confer ϕNPV1 resistance by blocking phage adsorption. We attribute the inability of the phage to adsorb to the modification or loss of an extracellular polymer in strains with inactivated Phage-resistant mutants exhibited increased daptomycin and osmotic stress susceptibilities. Our results demonstrate that spontaneous resistance to ϕNPV1 comes at a cost in OG1RF.