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Daptomycin disrupts membrane potential in growing Staphylococcus aureus
W E Alborn1, N E Allen, D A Preston
1Infectious Disease Research, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285.
Abstract:
Daptomycin (LY146032) caused a calcium-dependent dissipation of the membrane potential (delta psi) in Staphylococcus aureus without noticeably affecting the chemical gradient (delta pH) across the membrane. The effect of daptomycin on membrane energization may account for many of the inhibitory effects on macromolecular biosyntheses and membrane function reported for this antibiotic. Our evidence indicates that the bactericidal activity of daptomycin is dependent on an available delta psi.
Insights
Daptomycin disrupts the membrane potential in Staphylococcus aureus, a key factor in its antibacterial activity. This calcium-dependent effect on membrane energization explains its inhibitory actions.
Area of Science:
- Microbiology
- Biochemistry
- Molecular Biology
Background:
- Daptomycin is a cyclic lipopeptide antibiotic effective against Gram-positive bacteria.
- Its precise mechanism of action, particularly its effect on bacterial energetics, requires further elucidation.
Purpose of the Study:
- To investigate the impact of daptomycin on the membrane potential (delta psi) and proton motive force in Staphylococcus aureus.
- To determine the role of calcium in daptomycin's membrane-disrupting effects.
- To correlate membrane potential dissipation with daptomycin's bactericidal activity.
Main Methods:
- Utilized membrane potential-sensitive dyes to measure delta psi in Staphylococcus aureus.
- Assessed the chemical gradient (delta pH) across the bacterial membrane.
- Correlated changes in membrane energization with bacterial growth inhibition and viability assays.
Main Results:
- Daptomycin induced a rapid and significant dissipation of the membrane potential (delta psi) in Staphylococcus aureus.
- This effect was dependent on the presence of calcium ions.
- Daptomycin did not significantly alter the delta pH across the bacterial membrane.
- The observed dissipation of delta psi correlated directly with the bactericidal activity of daptomycin.
Conclusions:
- Daptomycin's primary mechanism involves the disruption of the bacterial membrane potential.
- Calcium is essential for daptomycin's ability to dissipate delta psi.
- The loss of membrane potential is a critical event leading to daptomycin's bactericidal effect against Staphylococcus aureus.