Antituberculosis drug interactions with membranes: A biophysical approach applied to bedaquiline

Marina Pinheiro*, Heinz Amenitsch, Salette Reis

*Corresponding author for this work

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Article number141
JournalMembranes
Volume9
Issue number11
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • Antibiotic
  • Liposomes
  • Membrane models
  • SAXS
  • Tuberculosis
  • WAXS

ASJC Scopus subject areas

  • Chemical Engineering (miscellaneous)
  • Process Chemistry and Technology
  • Filtration and Separation

Fields of Expertise

  • Human- & Biotechnology

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