Mechanisms of Daptomycin Resistance in Staphylococcus Aureus

Int J Antimicrob Agents. 2006 Oct;28(4):280-7. doi: 10.1016/j.ijantimicag.2006.05.030. Epub 2006 Sep 11.

Abstract

Daptomycin resistance in Staphylococcus aureus emerged during therapy of tricuspid endocarditis. Susceptibility to daptomycin of the parent strain (SA-675), other daptomycin-susceptible strains and the non-susceptible mutant (SA-684) was heterogeneous; however, subpopulations growing at concentrations above the minimum inhibitory concentration (MIC) were not stably resistant. Stable resistance was produced only by serial passage on daptomycin-containing media. Daptomycin dissipated the membrane potential of SA-675 but not SA-684, which also lost an 81 kDa membrane protein. Whole cells and membranes of SA-684 bound a reduced amount of daptomycin. Reduced drug binding in SA-684 correlates with daptomycin resistance, possibly as a result of the loss of a membrane protein 'chaperone' with which daptomycin interacts. Heterogeneity of daptomycin MICs in susceptible strains may be an important factor in the development of stable, clinically relevant resistance.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Daptomycin / pharmacology*
  • Daptomycin / therapeutic use
  • Drug Resistance, Bacterial*
  • Microbial Sensitivity Tests
  • Staphylococcal Infections / drug therapy
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / genetics

Substances

  • Daptomycin