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Enterococci are a part of human microbiota and a leading cause of multidrug resistant infections. Here, we identify a family of Enterococcus pore-forming toxins (Epxs)) in E. faecalis, E. faecium, and E. hirae strains isolated across the globe. Structural studies reveal that Epxs form a branch of beta-barrel pore-forming toxins with a beta-barrel protrusion (designated the top domain) sitting atop the cap d…