Membrane activity of the pentaene macrolide didehydroroflamycoin in 2 model lipid bilayers

0436047 - ÚFCH JH 2016 RIV NL eng J - Journal Article
Koukalová, Alena - Pokorná, Šárka - Fišer, Radovan - Kopecký, Jr., V. - Humpolíčková, Jana - Černý, J. - Hof, Martin
Membrane activity of the pentaene macrolide didehydroroflamycoin in 2 model lipid bilayers.
Biochimica Et Biophysica Acta-Biomembranes. Roč. 1848, č. 2 (2015), s. 444-452. ISSN 0005-2736. E-ISSN 1879-2642
R&D Projects: GA ČR(CZ) GC14-03141J; GA MŠMT LH13259
Institutional support: RVO:61388955 ; RVO:61388971
Keywords : Didehydroroflamycoin * Filipin III * Amphotericin B
Subject RIV: CF - Physical ; Theoretical Chemistry
Impact factor: 3.687, year: 2015

Didehydroroflamycoin (DDHR), a recently isolatedmember of the polyenemacrolide family, was shown to have 21 antibacterial and antifungal activity. However, its mechanism of action has not been investigated. Antibiotics 22 from this family are amphiphilic; thus, they have membrane activity, their biological action is localized in the 23 membrane, and the membrane composition and physical properties facilitate the recognition of a particular 24 compound by the target organism. In this work, we use model lipid membranes comprised of giant unilamellar 25 vesicles (GUVs) for a systematic study of the action of DDHR. In parallel, experiments are conducted using filipin 26 III and amphotericin B, other members of the family, and the behavior observed for DDHR is described in the 27 context of that of these two heavily studied compounds. The study shows that DDHR disrupts membranes via 28 two different mechanisms and that the involvement of these mechanisms depends on the presence of 29 cholesterol. The leakage assays performed in GUVs and the conductance measurements using black lipid 30 membranes (BLM) reveal that the pores that develop in the absence of cholesterol are transient and their size 31 is dependent on the DDHR concentration. In contrast, cholesterol promotes the formation of more defined 32 structures that are temporally stable.
Permanent Link: http://hdl.handle.net/11104/0239913