Cell wall thickening is not a universal accompaniment of the daptomycin nonsusceptibility phenotype in Staphylococcus aureus: evidence for multiple resistance mechanisms.

Abstract:

: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-resistant Staphylococcus 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 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 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 among S. aureus strains.

authors

Yang SJ,Nast CC,Mishra NN,Yeaman MR,Fey PD,Bayer AS

doi

10.1128/AAC.00122-10

subject

Has Abstract

pub_date

2010-08-01 00:00:00

pages

3079-85

issue

8

eissn

0066-4804

issn

1098-6596

pii

AAC.00122-10

journal_volume

54

pub_type

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