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 concentratio...

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Bibliographic Details
Published in:International journal of antimicrobial agents 2006-10, Vol.28 (4), p.280-287
Main Authors: Kaatz, Glenn W., Lundstrom, Tammy S., Seo, Susan M.
Format: Article
Language:English
Subjects:
Antibacterial agents
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antimicrobial resistance
Biological and medical sciences
Daptomycin
Daptomycin - pharmacology
Daptomycin - therapeutic use
Drug Resistance, Bacterial
Medical sciences
Microbial Sensitivity Tests
Pharmacology. Drug treatments
Staphylococcal Infections - drug therapy
Staphylococcus aureus
Staphylococcus aureus - drug effects
Staphylococcus aureus - genetics
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Summary: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.
ISSN:0924-8579
1872-7913
DOI:10.1016/j.ijantimicag.2006.05.030