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Nanomechanics of Drug-target Interactions and Antibacterial Resistance Detection
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Daptomycin resistance in enterococci is associated with distinct alterations of cell membrane phospholipid content

Nagendra N Mishra1, Arnold S Bayer, Truc T Tran

  • 1Division of Infectious Diseases, Los Angeles Biomedical Research Institute at Harbor-University of California Los Angeles Medical Center, Torrance, California, United States of America.

Plos One
|September 7, 2012
PubMed
Abstract

Insights

Daptomycin resistance in enterococci is linked to changes in cell membrane phospholipids, specifically reduced fluidity and phosphatidylglycerol, with increased glycerolphospho-diglycodiacylglycerol. These alterations impact membrane function and antibiotic susceptibility.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Biochemistry

Background:

  • Daptomycin (DAP) is a lipopeptide antibiotic targeting bacterial cell membranes.
  • DAP resistance in Enterococcus faecalis is linked to cell envelope and phospholipid metabolism gene mutations.
  • This study investigates changes in cell membrane phospholipid profiles during DAP resistance development in clinical enterococcal strains.

Purpose of the Study:

  • To characterize alterations in cell membrane phospholipid content and composition associated with daptomycin resistance in clinical Enterococcus strains.
  • To compare membrane fluidity, permeability, and depolarization capacity between daptomycin-susceptible and resistant strains.
  • To examine cell envelope structural changes and cell surface charge in relation to daptomycin resistance.

Main Methods:

  • Comparative analysis of phospholipid profiles (content, fatty acid composition) in susceptible and resistant E. faecalis and E. faecium strains.
  • Assessment of membrane fluidity, DAP-induced permeabilization, and depolarization.
  • Transmission electron microscopy for cell envelope characterization and measurement of relative cell surface charge.

Main Results:

  • Daptomycin resistance correlated with decreased membrane fluidity, reduced phosphatidylglycerol (PG), and increased glycerolphospho-diglycodiacylglycerol (GP-DGDAG) in both species.
  • E. faecium showed decreased unsaturated fatty acids and structural cell envelope alterations, including cell wall thickening.
  • Daptomycin-resistant E. faecium exhibited reduced membrane depolarization and permeabilization by DAP.

Conclusions:

  • Significant changes in phospholipid content and fatty acid composition are key factors in the development of enterococcal daptomycin resistance.
  • These membrane alterations contribute to reduced susceptibility and altered membrane function in daptomycin-resistant enterococci.
  • Understanding these mechanisms is crucial for developing strategies to combat antibiotic resistance.

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