title: Genotypic and phenotypic evaluation of the evolution of high-level daptomycin nonsusceptibility in vancomycin-resistant Enterococcus faecium.
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.
authors.affiliation: Department of Pathology & Laboratory Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA. rhumphries@mednet.ucla.edu
authors.forename: Romney M
authors.initials: RM
authors.lastname: Humphries
authors.forename: Theodoros
authors.initials: T
authors.lastname: Kelesidis
authors.forename: Ryan
authors.initials: R
authors.lastname: Tewhey
authors.forename: Warren E
authors.initials: WE
authors.lastname: Rose
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schork
authors.forename: Victor
authors.initials: V
authors.lastname: Nizet
authors.forename: George
authors.initials: G
authors.lastname: Sakoulas
mesh_terms: D000222:Adaptation, Physiological / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D002999:Clone Cells; D017576:Daptomycin / Q000494:pharmacology*; D016984:Enterococcus faecium / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D005838:Genotype; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D016366:Open Reading Frames / Q000235:genetics; D010641:Phenotype; D010770:Phosphotransferases / Q000235:genetics / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D055672:Static Electricity; D017855:Transferases (Other Substituted Phosphate Groups) / Q000235:genetics / Q000378:metabolism; D014640:Vancomycin / Q000494:pharmacology*; D020713:Vancomycin Resistance / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D008565:Membrane Proteins; D014640:Vancomycin; D010770:Phosphotransferases; D017855:Transferases (Other Substituted Phosphate Groups); C100091:cardiolipin synthetase; D017576:Daptomycin