Genotypic and phenotypic evaluation of the evolution of high-level daptomycin nonsusceptibility in vancomycin-resistant Enterococcus faecium

Antimicrob Agents Chemother. 2012 Nov;56(11):6051-3. doi: 10.1128/AAC.01318-12. Epub 2012 Sep 4.

Abstract

Whole-genome sequencing and cell membrane studies of three clonal Enterococcus faecium strains with daptomycin MICs of 4, 32, and 192 μg/ml were performed, revealing nonsynonymous single nucleotide variants in eight open reading frames, including those predicted to encode a phosphoenolpyruvate-dependent, mannose-specific phosphotransferase system, cardiolipin synthetase, and EzrA. Membrane studies revealed a higher net surface charge among the daptomycin-nonsusceptible isolates and increased septum formation in the isolate with a daptomycin MIC of 192 μg/ml.

Publication types

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

MeSH terms

  • Adaptation, Physiological / genetics
  • Anti-Bacterial Agents / pharmacology*
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Cell Membrane / drug effects
  • Cell Membrane / genetics*
  • Cell Membrane / metabolism
  • Clone Cells
  • Daptomycin / pharmacology*
  • Enterococcus faecium / drug effects
  • Enterococcus faecium / genetics*
  • Enterococcus faecium / metabolism
  • Genotype
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Microbial Sensitivity Tests
  • Open Reading Frames / genetics
  • Phenotype
  • Phosphotransferases / genetics
  • Phosphotransferases / metabolism
  • Polymorphism, Single Nucleotide
  • Static Electricity
  • Transferases (Other Substituted Phosphate Groups) / genetics
  • Transferases (Other Substituted Phosphate Groups) / metabolism
  • Vancomycin / pharmacology*
  • Vancomycin Resistance / genetics

Substances

  • Anti-Bacterial Agents
  • Bacterial Proteins
  • Membrane Proteins
  • Vancomycin
  • Phosphotransferases
  • Transferases (Other Substituted Phosphate Groups)
  • cardiolipin synthetase
  • Daptomycin