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Interaction of duramycin with artificial and natural membranes
Abstract:
Duramycin is a polypeptide antibiotic (molecular weight 2012) obtained from culture filtrates of Streptomyces cinnamomeus forma azacoluta. In this work, we show that low concentrations of duramycin induced aggregation of lipid vesicles containing unsaturated phosphatidylethanolamine and unsaturated monogalactosyl diglyceride, and of sarcoplasmic reticulum vesicles from rabbit skeletal muscle. Furthermore, duramycin inhibited the ATP-dependent Ca2+ uptake in sarcoplasmic reticulum vesicles without affecting the hydrolysis of ATP or the permeability of Ca2+. Also, duramycin only inhibited the bacteriorhodopsin proton pump reconstituted into phospholipid vesicles containing phosphatidylethanolamine. We have isolated a duramycin-resistant strain of Bacillus subtilis and have mapped the location of duramycin resistance. In this strain, the secretion of protons and influx of calcium were resistant to duramycin, and its lipid composition was profoundly different from that of the parent strain. No phosphatidylethanolamine was detected in the resistant strain. Our findings are consistent with the idea that duramycin recognizes a particular membrane conformation determined by the presence of phosphatidylethanolamine or monogalactosyl diglyceride.
Insights
Duramycin, an antibiotic, aggregates lipid vesicles and inhibits calcium uptake by interacting with phosphatidylethanolamine. Resistance emerged when this lipid was absent, confirming duramycin
Area of Science:
- Biochemistry
- Molecular Biology
- Microbiology
Background:
- Duramycin is a polypeptide antibiotic derived from Streptomyces cinnamomeus.
- Its mechanism of action on biological membranes is not fully understood.
Purpose of the Study:
- To investigate the molecular interactions of duramycin with lipid membranes.
- To elucidate the role of specific lipids in duramycin's biological activity.
Main Methods:
- Lipid vesicle aggregation assays.
- Measurement of ATP-dependent Ca2+ uptake in sarcoplasmic reticulum vesicles.
- Reconstitution of bacteriorhodopsin proton pump.
- Isolation and characterization of a duramycin-resistant bacterial strain.
Main Results:
- Duramycin induced aggregation of vesicles containing unsaturated phosphatidylethanolamine (PE) and monogalactosyl diglyceride (MGDG).
- It inhibited Ca2+ uptake in sarcoplasmic reticulum vesicles without affecting ATP hydrolysis.
- Duramycin selectively inhibited the bacteriorhodopsin proton pump in PE-containing vesicles.
- A duramycin-resistant Bacillus subtilis strain lacked PE and showed resistance to duramycin's effects.
Conclusions:
- Duramycin's activity is dependent on the presence of specific membrane lipids, particularly phosphatidylethanolamine.
- The antibiotic likely recognizes a specific membrane conformation induced by PE or MGDG.
- Lipid composition is crucial for cellular susceptibility to duramycin.