Membrane activity of the pentaene macrolide didehydroroflamycoin in model lipid bilayers

作者：Koukalova Alena; Pokorna Sarka; Fiser Radovan; Kopecky Vladimir Jr; Humpolickova Jana^*; Cerny Jan; Hof Martin

来源：Biochimica et Biophysica Acta-Biomembranes, 2015, 1848(2): 444-452.

DOI：10.1016/j.bbamem.2014.10.038

• Didehydroroflamycoin
• Filipin III
• Amphotericin B
• Giant unilamellar vesicles
• Cholesterol

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.

• 出版日期2015-2