TY - JOUR
T1 - Cell wall thickening is not a universal accompaniment of the daptomycin nonsusceptibility phenotype in Staphylococcus aureus
T2 - Evidence for multiple resistance mechanisms
AU - Yang, Soo Jin
AU - Nast, Cynthia C.
AU - Mishra, Nagendra N.
AU - Yeaman, Michael R.
AU - Fey, Paul D.
AU - Bayer, Arnold S.
PY - 2010/8/1
Y1 - 2010/8/1
N2 - The mechanism(s) of daptomycin (DAP) resistance (DAP r) 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-resistant Staphylococcus aureus (MRSA) isolates (pulsotype USA 300) from the bloodstream of a DAP-treated patient with endocarditis in which serial strains exhibited increasing DAP r. Of interest, the DAP r isolate differed from its parental strain in several parameters, including acquisition of a point mutation within the putative synthase domain of the mprF gene in association with enhanced mprF 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 DAP r isolates (MRSA 11/21 and REF2145) compared with that in the DAP-susceptible (DAP s) 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 DAP s/DAP r S. aureus strain pairs, only three DAP r isolates exhibited CWs significantly thicker than those of the respective DAP s parent. These data confirm that CW thickening is neither universal to DAP r S. aureus nor sufficient to yield the DAPr phenotype among S. aureus strains.
AB - The mechanism(s) of daptomycin (DAP) resistance (DAP r) 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-resistant Staphylococcus aureus (MRSA) isolates (pulsotype USA 300) from the bloodstream of a DAP-treated patient with endocarditis in which serial strains exhibited increasing DAP r. Of interest, the DAP r isolate differed from its parental strain in several parameters, including acquisition of a point mutation within the putative synthase domain of the mprF gene in association with enhanced mprF 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 DAP r isolates (MRSA 11/21 and REF2145) compared with that in the DAP-susceptible (DAP s) 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 DAP s/DAP r S. aureus strain pairs, only three DAP r isolates exhibited CWs significantly thicker than those of the respective DAP s parent. These data confirm that CW thickening is neither universal to DAP r S. aureus nor sufficient to yield the DAPr phenotype among S. aureus strains.
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U2 - 10.1128/AAC.00122-10
DO - 10.1128/AAC.00122-10
M3 - Article
C2 - 20498310
AN - SCOPUS:77955352834
SN - 0066-4804
VL - 54
SP - 3079
EP - 3085
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
IS - 8
ER -