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

Soo Jin Yang, Cynthia C. Nast, Nagendra N. Mishra, Michael R. Yeaman, Paul D. Fey, Arnold S. Bayer

Research output: Contribution to journalArticlepeer-review

85 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3079-3085
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume54
Issue number8
DOIs
StatePublished - Aug 1 2010

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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