Open AccessCell Wall Thickening Is Not a Universal Accompaniment of the Daptomycin Nonsusceptibility Phenotype in Staphylococcus aureus : Evidence for Multiple Resistance Mechanisms
Author(s) -
Soo Jin Yang,
Cynthia C. Nast,
Nagendra N. Mishra,
Michael R. Yeaman,
Paul D. Fey,
Arnold S. Bayer
Publication year - 2010
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.00122-10
Subject(s) - daptomycin , staphylococcus aureus , thickening , microbiology and biotechnology , phenotype , cell wall , biology , bacteria , chemistry , vancomycin , gene , genetics , polymer science
The mechanism(s) of daptomycin (DAP) resistance (DAPr ) is incompletely defined. Thickened cell walls (CWs) acting as either a mechanical barrier or an affinity trap for DAP have been purported to be a major contributor to the DAPr phenotype. To this end, we studied an isogenic set of methicillin-resistantStaphylococcus aureus (MRSA) isolates (pulsotype USA 300) from the bloodstream of a DAP-treated patient with endocarditis in which serial strains exhibited increasing DAPr . Of interest, the DAPr isolate differed from its parental strain in several parameters, including acquisition of a point mutation within the putative synthase domain of themprF gene in association with enhancedmprF expression, increased synthesis of lysyl-phosphotidylglycerol, an enhanced positive envelope charge, and reduced DAP surface binding. Transmission electron microscopy (TEM) revealed no significant increases in CW thickness in the two DAPr isolates (MRSA 11/21 and REF2145) compared with that in the DAP-susceptible (DAPs ) parental strain, MRSA 11/11. The rates of Triton X-100-induced autolysis were also identical for the strain set. Furthermore, among six additional clinically isolated DAPs /DAPr S. aureus strain pairs, only three DAPr isolates exhibited CWs significantly thicker than those of the respective DAPs parent. These data confirm that CW thickening is neither universal to DAPr S. aureus nor sufficient to yield the DAPr phenotype amongS. aureus strains.