Loss-of-Function Mutations in <i>epaR</i> Confer Resistance to ϕNPV1 Infection in Enterococcus faecalis OG1RF

Abstract

<i>Enterococcus faecalis</i> is a Gram-positive opportunistic pathogen that inhabits the human gastrointestinal tract. Because of the high frequency of antibiotic resistance among <i>Enterococcus</i> clinical isolates, interest in using phage to treat enterococcal infections and to decolonize high-risk patients for antibiotic-resistant <i>Enterococcus</i> is rising. Bacteria can evolve phage resistance, but there is little published information on these mechanisms in <i>E. faecalis</i> In this report, we identified genetic determinants of <i>E. faecalis</i> resistance to phage NPV1 (ϕNPV1). We found that loss-of-function mutations in <i>epaR</i> 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 <i>epaR</i> Phage-resistant <i>epaR</i> mutants exhibited increased daptomycin and osmotic stress susceptibilities. Our results demonstrate that <i>in vitro</i> spontaneous resistance to ϕNPV1 comes at a cost in <i>E. faecalis</i> OG1RF.