Mechanisms of daptomycin resistance in Staphylococcus aureus.
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.
Kaatz
Glenn W
GW
The John D. Dingell Department of Veteran's Affairs Medical Center, Wayne State University School of Medicine, Detroit, MI 48201, USA. gkaatz@juno.com
Lundstrom
Tammy S
TS
Seo
Susan M
SM
D017576:Daptomycin / Q000494:pharmacology* / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D008826:Microbial Sensitivity Tests; D013203:Staphylococcal Infections / Q000188:drug therapy; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics
D017576:Daptomycin