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Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline

This work focuses on the interaction of the novel and representative antituberculosis (anti-TB) drug bedaquiline (BDQ) with different membrane models of eukaryotic and prokaryotic cells. The effect of BDQ on eukaryotic cell membrane models was assessed using liposomes, namely, multilamellar vesicles...

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Autores principales: Pinheiro, Marina, Amenitsch, Heinz, Reis, Salette
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918463/
https://www.ncbi.nlm.nih.gov/pubmed/31671599
http://dx.doi.org/10.3390/membranes9110141
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author Pinheiro, Marina
Amenitsch, Heinz
Reis, Salette
author_facet Pinheiro, Marina
Amenitsch, Heinz
Reis, Salette
author_sort Pinheiro, Marina
collection PubMed
description This work focuses on the interaction of the novel and representative antituberculosis (anti-TB) drug bedaquiline (BDQ) with different membrane models of eukaryotic and prokaryotic cells. The effect of BDQ on eukaryotic cell membrane models was assessed using liposomes, namely, multilamellar vesicles (MLVs) made of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) and also a mixture of DMPC and cholesterol (CHOL) (8:2 molar ratio). To mimic the prokaryotic cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and 1,1′2,2′-tetra-oleoyl-cardiolipin (TOCL) were chosen. Powerful biophysical techniques were employed, including small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), to understand the effect of BDQ on the nanostructure of the membrane models. The results showed that BDQ demonstrated a pronounced disordering effect in the bacterial cell membrane models, especially in the membrane model with cardiolipin (CL), while the human cell membrane model with large fractions of neutral phospholipids remained less affected. The membrane models and techniques provide detailed information about different aspects of the drug–membrane interaction, thus offering valuable information to better understand the effect of BDQ on their target membrane-associated enzyme as well as its side effects on the cardiovascular system.
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spelling pubmed-69184632019-12-24 Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline Pinheiro, Marina Amenitsch, Heinz Reis, Salette Membranes (Basel) Article This work focuses on the interaction of the novel and representative antituberculosis (anti-TB) drug bedaquiline (BDQ) with different membrane models of eukaryotic and prokaryotic cells. The effect of BDQ on eukaryotic cell membrane models was assessed using liposomes, namely, multilamellar vesicles (MLVs) made of 1,2-dimyristoyl-rac-glycero-3-phosphocholine (DMPC) and also a mixture of DMPC and cholesterol (CHOL) (8:2 molar ratio). To mimic the prokaryotic cell membrane, 1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (DMPG) and 1,1′2,2′-tetra-oleoyl-cardiolipin (TOCL) were chosen. Powerful biophysical techniques were employed, including small-angle X-ray scattering (SAXS) and wide-angle X-ray scattering (WAXS), to understand the effect of BDQ on the nanostructure of the membrane models. The results showed that BDQ demonstrated a pronounced disordering effect in the bacterial cell membrane models, especially in the membrane model with cardiolipin (CL), while the human cell membrane model with large fractions of neutral phospholipids remained less affected. The membrane models and techniques provide detailed information about different aspects of the drug–membrane interaction, thus offering valuable information to better understand the effect of BDQ on their target membrane-associated enzyme as well as its side effects on the cardiovascular system. MDPI 2019-10-30 /pmc/articles/PMC6918463/ /pubmed/31671599 http://dx.doi.org/10.3390/membranes9110141 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pinheiro, Marina
Amenitsch, Heinz
Reis, Salette
Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline
title Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline
title_full Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline
title_fullStr Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline
title_full_unstemmed Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline
title_short Antituberculosis Drug Interactions with Membranes: A Biophysical Approach Applied to Bedaquiline
title_sort antituberculosis drug interactions with membranes: a biophysical approach applied to bedaquiline
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6918463/
https://www.ncbi.nlm.nih.gov/pubmed/31671599
http://dx.doi.org/10.3390/membranes9110141
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