Phage-resistance of Salmonella enterica serovar Enteritidis and pathogenesis in Caenorhabditis elegans is mediated by the lipopolysaccharide

*Corresponding author Phage therapy has been used in the past as an alternative therapy against bacterial pathogens. However, phage-resistant bacterial strains can emerge. Some studies show that these phage-resistant strains are avirulent. In this study, we report that phage-resistant strains of Salmonella enterica serovar Enteritidis (hereafter S. Enteritidis) were avirulent in the Caenorhabditis elegans animal model. We isolated phage-resistant strains of S. Enteritidis ATCC 13076 by using three lytic phages (f2αSE, f3αSE and f18αSE). In these mutants, we explored different virulence factors like lipopolysaccharide (LPS), virulence plasmid (Pla), motility and type I fimbriae, all of which may have effects on virulence and could furthermore be related to phage resistance. The phage-resistant strains of S. Enteritidis showed loss of O-Polysaccharide (O-PS) and auto-agglutination, present a rough phenotype and consequently they are avirulent in the C. elegans animal model. We speculate that the O-PS is necessary for phage attachment to the S. Enteritidis cell surface.