Structure-Activity Relationships of the Enterococcal Cytolysin

Imran R. Rahman, Alondra Sanchez, Weixin Tang, Wilfred A. Van Der Donk

Research output: Contribution to journalArticlepeer-review


Enterococcal cytolysin is a hemolytic virulence factor linked to human disease and increased patient mortality. Produced by pathogenic strains of Enterococcus faecalis, cytolysin is made up of two small, post-translationally modified peptides called CylLL"and CylLS". They exhibit a unique toxicity profile where lytic activity is observed for both mammalian cells and Gram-positive bacteria that is dependent on the presence of both peptides. In this study, we performed alanine substitution of all residues in CylLL"and CylLS"and determined the effect on both activities. We identified key residues involved in overall activity and residues that dictate cell type specificity. All (methyl)lanthionines as well as a Gly-rich hinge region were critical for both activities. In addition, we investigated the binding of the two subunits to bacterial cells suggesting that the large subunit CylLL"has stronger affinity for the membrane or a target molecule therein. Genome mining identified other potential two-component lanthipeptides and provided insights into potential evolutionary origins.

Original languageEnglish (US)
Pages (from-to)2445-2454
Number of pages10
JournalACS Infectious Diseases
Issue number8
StatePublished - Aug 13 2021


  • E. faecalis
  • RiPP
  • antibiotic
  • hemolysis
  • lanthipeptide
  • lantibiotic
  • liver disease
  • peptide stapling

ASJC Scopus subject areas

  • Infectious Diseases


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