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

Antimicrob Agents Chemother. 2010 Oct;54(10):4476-9. doi: 10.1128/AAC.00191-10. Epub 2010 Jul 26.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry*
  • Anti-Bacterial Agents / pharmacology
  • Antimicrobial Cationic Peptides / chemistry*
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects
  • Daptomycin / chemistry*
  • Daptomycin / pharmacology
  • Drug Resistance, Bacterial
  • Lipid Bilayers / chemistry*
  • Lysine / chemistry*
  • Phosphatidylglycerols / chemistry*
  • Phospholipids / chemistry

Substances

  • Anti-Bacterial Agents
  • Antimicrobial Cationic Peptides
  • Lipid Bilayers
  • Phosphatidylglycerols
  • Phospholipids
  • lysylphosphatidylglycerol
  • Lysine
  • Daptomycin