title: Lysyl-phosphatidylglycerol attenuates membrane perturbation rather than surface association of the cationic antimicrobial peptide 6W-RP-1 in a model membrane system: implications for daptomycin resistance.
abstract: The presence of the cationic phospholipid lysyl-phosphatidylglycerol (lysyl-PG) in staphylococcal cytoplasmic membranes has been linked to increased resistance to cationic compounds, including antibiotics such as daptomycin as well as host defense antimicrobial peptides. We investigated the effects of lysyl-PG on binding of 6W-RP-1, a synthetic antimicrobial peptide, to lipid vesicles and on peptide-induced membrane permeabilization. Unexpectedly, physiological lysyl-PG concentrations only minimally reduced membrane binding of 6W-RP-1. In contrast, 6W-RP-1-induced dye leakage was severely inhibited by lysyl-PG, suggesting that lysyl-PG primarily impacts membrane defect formation.
authors.affiliation: Department of Chemistry and Biochemistry, University of North Carolina Wilmington, Wilmington, North Carolina 28403, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Kilelee
authors.forename: Antje
authors.initials: A
authors.lastname: Pokorny
authors.forename: Michael R
authors.initials: MR
authors.lastname: Yeaman
authors.forename: Arnold S
authors.initials: AS
authors.lastname: Bayer
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects; D017576:Daptomycin / Q000737:chemistry* / Q000494:pharmacology; D024881:Drug Resistance, Bacterial; D008051:Lipid Bilayers / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry*; D010715:Phosphatidylglycerols / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008051:Lipid Bilayers; D010715:Phosphatidylglycerols; D010743:Phospholipids; C002285:lysylphosphatidylglycerol; D008239:Lysine; D017576:Daptomycin