Genotypic and Phenotypic Evaluation of the Evolution of High-Level Daptomycin Nonsusceptibility in Vancomycin-Resistant Enterococcus faecium
Author(s) -
Romney M. Humphries,
Theodoros Kelesidis,
Ryan Tewhey,
Warren E. Rose,
Nicholas J. Schork,
Victor Nizet,
George Sakoulas
Publication year - 2012
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.01318-12
Subject(s) - daptomycin , enterococcus faecium , enterococcus , genotype , vancomycin , microbiology and biotechnology , biology , vancomycin resistant enterococcus , drug resistance , antibiotics , bacteria , genetics , gene , staphylococcus aureus
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.
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