Efaginas evolucionadas independientemente para atacar la pared celular de enterococos

Enterococci are major causes of multidrug-resistant hospital infections, underscoring the need for new antibacterial strategies. Here, we describe a previously unrecognized inhibitor class, efagins ( E nterococcus f aecalis phage-related inhibitors). Efagins are intrinsic to E. faecalis, the most widely distributed generalist among enterococci, and are structurally reminiscent of phage tails yet show only distant evolutionary relatedness to known phages or phage-like elements. The 14.6-kb efagin gene cluster is highly conserved except for a tail fiber-like encoding region that varies across five distinct classes. These classes correlate with differences in the rhamnose-rich Epa cell wall polysaccharide, the efagin binding target as demonstrated by domain-swap experiments. We identified at least 20 E. faecalis epa genotypes, and the efagins characterized here inhibit strains representing 17 of them. Importantly, efagin activity extends beyond E. faecalis: they inhibit multiple enterococcal species, including lineages of vancomycin-resistant E. faecium, highlighting their potential as precision antibacterials.