Daptomycin Pore Formation and Stoichiometry Depend on Membrane Potential of Target Membrane

Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11310%2F19%3A10385875" target="_blank" >RIV/00216208:11310/19:10385875 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1128/AAC.01589-18" target="_blank" >https://doi.org/10.1128/AAC.01589-18</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1128/AAC.01589-18" target="_blank" >10.1128/AAC.01589-18</a>

Result language
angličtina
Original language name
Daptomycin Pore Formation and Stoichiometry Depend on Membrane Potential of Target Membrane
Original language description
Daptomycin is a calcium-dependent lipodepsipeptide antibiotic clinically used to treat serious infections caused by Gram-positive pathogens. Its precise mode of action is somewhat controversial; the biggest issue is daptomycin pore formation, which we directly investigated here. We first performed a screening experiment using propidium iodide (PI) entry to Bacillus subtilis cells and chose the optimum and therapeutically relevant conditions (10 mu g/ml daptomycin and 1.25 mM CaCl2) for the subsequent analyses. Using conductance measurements on planar lipid bilayers, we show that daptomycin forms nonuniform oligomeric pores with conductance ranging from 120 pS to 14 nS. The smallest conductance unit is probably a dimer; however, tetramers and pentamers occur in the membrane most frequently. Moreover, daptomycin pore-forming activity is exponentially dependent on the applied membrane voltage. We further analyzed the membrane-permeabilizing activity in B. subtilis cells using fluorescence methods [PI and DiSC(3)(5)]. Daptomycin most rapidly permeabilizes cells with high initial membrane potential and dissipates it within a few minutes. Low initial membrane potential hinders daptomycin pore formation.
Czech name
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Czech description
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Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
—
OECD FORD branch
10606 - Microbiology

Project
<a href="/en/project/GA15-01687S" target="_blank" >GA15-01687S: Allotropes of carbon: microbiological studies</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

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