Comparison of the Effects of Daptomycin on Bacterial and Model Membranes

Biochemistry
Ming-Tao LeeHuey W Huang

Abstract

Daptomycin is a phosphatidylglycerol specific, calcium-dependent membrane-active antibiotic that has been approved for the treatment of Gram-positive infections. A recent Bacillus subtilis study found that daptomycin clustered into fluid lipid domains of bacterial membranes and the membrane binding was correlated with dislocation of peripheral membrane proteins and depolarization of membrane potential. In particular, the study disproved the existence of daptomycin ion channels. Our purpose here is to study how daptomycin interacts with lipid bilayers to understand the observed phenomena on bacterial membranes. We performed new types of experiments using aspirated giant vesicles with an ion leakage indicator, making comparisons between daptomycin and ionomycin, performing vesicle-vesicle transfers, and measuring daptomycin binding to fluid phase versus gel phase bilayers and bilayers including cholesterol. Our findings are entirely consistent with the observations for bacterial membranes. In addition, daptomycin is found to cause ion leakage through the membrane only if its concentration in the membrane is over a certain threshold. The ion leakage caused by daptomycin is transient. It occurs only when daptomycin binds the membra...Continue Reading

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Citations

Jan 17, 2020·Antibiotics·Charles H Chen, Timothy K Lu
Jun 4, 2020·Probiotics and Antimicrobial Proteins·Ping-Ping TianYuan-Sen Hu
Feb 3, 2021·The Journal of Microbiology·Minkyung RyuKangseok Lee
Feb 24, 2021·The Journal of Membrane Biology·Antje Pokorny, Paulo F Almeida
Jun 12, 2020·Biochimica Et Biophysica Acta. Biomembranes·Huey W Huang
Sep 5, 2020·The Journal of Physical Chemistry. B·Andrea MescolaAndrea Alessandrini
Nov 30, 2021·Angewandte Chemie·Ryan Moreira, Scott D Taylor
Dec 7, 2021·Frontiers in Nutrition·Qun WangYong Cao
Feb 5, 2022·Microbiology·Elizabeth V K LedgerAndrew M Edwards

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