Binding of Daptomycin to Anionic Lipid Vesicles Is Reduced in the Presence of Lysyl-Phosphatidylglycerol

Tala O Khatib; Heather Stevenson; Michael R Yeaman; Arnold S Bayer; Antje Pokorny

doi:10.1128/AAC.00744-16

Binding of Daptomycin to Anionic Lipid Vesicles Is Reduced in the Presence of Lysyl-Phosphatidylglycerol

Antimicrob Agents Chemother. 2016 Jul 22;60(8):5051-3. doi: 10.1128/AAC.00744-16. Print 2016 Aug.

Authors

Tala O Khatib¹, Heather Stevenson¹, Michael R Yeaman², Arnold S Bayer³, Antje Pokorny⁴

Affiliations

¹ University of North Carolina Wilmington, Department of Chemistry and Biochemistry, Wilmington, North Carolina, USA.
² Divisions of Molecular Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA Division of Adult Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, California, USA.
³ Divisions of Molecular Medicine, Los Angeles Biomedical Research Institute at Harbor-University of California at Los Angeles Medical Center, Torrance, California, USA.
⁴ University of North Carolina Wilmington, Department of Chemistry and Biochemistry, Wilmington, North Carolina, USA almeidaa@uncw.edu.

Abstract

The cytoplasmic membrane of Staphylococcus aureus contains ∼20 mol% of the net cationic lipid lysyl-phosphatidylglycerol (LPG). Elevated fractions of LPG are associated with increased resistance to cationic antibiotics, including the lipopeptide daptomycin (DAP). Although the surface charge of the bacterial cytoplasmic membrane is altered by LPG, surface binding of DAP was found to be only moderately affected in anionic vesicles containing 20 mol% LPG. These results suggest that charge repulsion cannot fully explain LPG-mediated resistance to cationic peptides.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Cell Membrane / drug effects
Cell Membrane / metabolism
Daptomycin / chemistry*
Daptomycin / pharmacology*
Lipids / chemistry*
Lysine / chemistry*
Microbial Sensitivity Tests
Phosphatidylglycerols / chemistry*

Substances

Anti-Bacterial Agents
Lipids
Phosphatidylglycerols
lysylphosphatidylglycerol
Lysine
Daptomycin

Grants and funding

R01 AI039108/AI/NIAID NIH HHS/United States