In vitro bactericidal activities of daptomycin against Staphylococcus aureus and Enterococcus faecalis are not mediated by inhibition of lipoteichoic acid biosynthesis

Abstract

Previous studies have suggested that lipoteichoic acid biosynthesis inhibition is the mechanism of action of daptomycin. In this investigation, daptomycin inhibited all macromolecular synthesis in Staphylococcus aureus, Enterococcus faecalis, and Enterococcus hirae without kinetic or dose specificity for lipoteichoic acid. Daptomycin remained bactericidal in the absence of ongoing lipoteichoic acid synthesis. Inhibition of lipoteichoic acid synthesis is apparently not the mechanism of action of daptomycin in these pathogens.

FIG. 1.

Effect of daptomycin on the biosynthesis of LTA, lipids, and RNA in S. aureus. S. aureus ATCC 29213 was incubated with two times the MIC of daptomycin (A) or rifampin (B) at time zero. Data are plotted as the means ± standard deviations of triplicate experiments.

FIG. 2.

Effect of daptomycin biosynthesis of LTA and RNA in E. faecalis and E. hirae. Daptomycin at two times the MIC was added to E. faecalis (A) or E. hirae (B) cultures at time zero, following 10 min of labeling in the absence of drug. Data are plotted as the means ± standard deviations of triplicate experiments.

FIG. 3.

Growth arrest does not inhibit daptomycin bactericidal activity. Exponentially growing or rifampin-growth-arrested S. aureus (A) or E. faecalis (B) was incubated for 1 h with daptomycin (Dap), ciprofloxacin (Cipro), or rifampin (Rif) at eight times the MIC. Representative data are shown.