The Enterococcus faecalis cytolysin: a novel toxin active against eukaryotic and prokaryotic cells

The enterococcal cytolysin, a two‐peptide lytic system, is a divergent relative of a large family of toxins and bacteriocins secreted by pathogenic and non‐pathogenic Gram‐positive bacteria. This family includes the lantibiotics and streptolysin S. The enterococcal cytolysin is of interest because its activities enhance enterococcal virulence in infection models and, in epidemiological studies, it has been associated with patient mortality. The cytolysin is lethal for a broad range of prokaryotic and eukaryotic cells, and this activity requires two non‐identical, post‐translationally modified peptides. The smaller of the two peptides also plays a role in a quorum‐sensing autoinduction of the cytolysin operon. As a trait that is present in particularly virulent strains of Enterococcus faecalis, including strains that are resistant to multiple antibiotics, it serves as a model for testing the value of developing new virulence‐targeting therapeutics. Further, because of the interest in small membrane active peptides as therapeutics themselves, studies of the molecular structure/activity relationships for the cytolysin peptides are providing insights into the physical basis for prokaryotic versus eukaryotic cell targeting.