1.C.122 The Pore-forming delta-Hemolysin (Hld) Family
δ-(hemo)lysin, secreted by Staphylococcus aureus, is a 26-residue membrane active peptide that shares many common features with antimicrobial peptides (AMPs), but with a few unique features that differentiate itself from typical AMPs. In particular, δ-lysin has zero net charge, even though it has many charged residues, and it preferentially lyses eukaryotic cells over bacterial cells. King et al. 2016 presented the results of coarse-grained molecular dynamics simulations of δ-lysin interacting with a zwitterionic membrane over a wide range of peptide concentrations. When the peptide concentration is low, spontaneous dimerization of peptides is observed on the membrane surface, but deep insertion of peptides or pore formation was not observed. However, the calculated free energy of peptide insertion suggested that a small fraction of peptides is likely to be present inside the membrane at the peptide concentrations typically seen in dye efflux experiments. When the simulations with multiple peptides were carried out with a single pre-inserted transmembrane peptide, spontaneous pore formation occured with a peptide-to-lipid ratio (P/L) as low as P/L=1:42. Inter-peptide salt bridges among the transmembrane peptides seemed to play a role in creating compact pores with very low levels of hydration. The transmembrane peptides making up the pore were constantly pushed to the opposite side of the membrane when the mass imbalance between the two sides of membrane was significant. Thus, the pore is very dynamic, allowing multiple peptides to translocate across the membrane simultaneously (King et al. 2016).