Membrane activity of the pentaene macrolide didehydroroflamycoin in model lipid bilayers
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
25450349
DOI
10.1016/j.bbamem.2014.10.038
PII: S0005-2736(14)00373-3
Knihovny.cz E-zdroje
- Klíčová slova
- Amphotericin B, Cholesterol, Didehydroroflamycoin, Filipin III, Giant unilamellar vesicles,
- MeSH
- amfotericin B chemie MeSH
- antibakteriální látky chemie MeSH
- antifungální látky chemie MeSH
- cholesterol chemie MeSH
- filipin analogy a deriváty chemie MeSH
- kinetika MeSH
- lipidové dvojvrstvy chemie MeSH
- makrolidy chemie MeSH
- unilamelární lipozómy chemie MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 32,33-didehydroroflamycoin MeSH Prohlížeč
- amfotericin B MeSH
- antibakteriální látky MeSH
- antifungální látky MeSH
- cholesterol MeSH
- filipin MeSH
- lipidové dvojvrstvy MeSH
- makrolidy MeSH
- unilamelární lipozómy MeSH
Didehydroroflamycoin (DDHR), a recently isolated member of the polyene macrolide family, was shown to have antibacterial and antifungal activity. However, its mechanism of action has not been investigated. Antibiotics from this family are amphiphilic; thus, they have membrane activity, their biological action is localized in the membrane, and the membrane composition and physical properties facilitate the recognition of a particular compound by the target organism. In this work, we use model lipid membranes comprised of giant unilamellar vesicles (GUVs) for a systematic study of the action of DDHR. In parallel, experiments are conducted using filipin III and amphotericin B, other members of the family, and the behavior observed for DDHR is described in the context of that of these two heavily studied compounds. The study shows that DDHR disrupts membranes via two different mechanisms and that the involvement of these mechanisms depends on the presence of cholesterol. The leakage assays performed in GUVs and the conductance measurements using black lipid membranes (BLM) reveal that the pores that develop in the absence of cholesterol are transient and their size is dependent on the DDHR concentration. In contrast, cholesterol promotes the formation of more defined structures that are temporally stable.
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