Rhodomyrtone (Rom) is a membrane-active compound

• Published in: Biochimica et biophysica acta. Biomembranes 2018-05, Vol.1860 (5), p.1114-1124
• Main Authors: Saising, Jongkon, Nguyen, Minh-Thu, Härtner, Thomas, Ebner, Patrick, Al Mamun Bhuyan, Abdulla, Berscheid, Anne, Muehlenkamp, Melanie, Schäkermann, Sina, Kumari, Nimerta, Maier, Martin E., Voravuthikunchai, Supayang P., Bandow, Julia, Lang, Florian, Brötz-Oesterhelt, Heike, Götz, Friedrich
• Format: Article
• Language: English
• Subjects: Animals; Anti-Infective Agents - pharmacology; Antibiotic; Bacillus subtilis; BALB 3T3 Cells; Cells, Cultured; Gram-positive bacteria; HeLa Cells; Hemolysis - drug effects; Humans; Membrane active; Membrane Potentials - drug effects; Membranes - drug effects; Membranes - physiology; Mice; Microbial Sensitivity Tests; Rhodomyrtone; Staphylococcus; Staphylococcus aureus; Xanthones - pharmacology
• ISSN: 0005-2736; 1879-2642
• DOI: 10.1016/j.bbamem.2018.01.011

Particularly in Asia medicinal plants with antimicrobial activity are used for therapeutic purpose. One such plant-derived antibiotic is rhodomyrtone (Rom) isolated from Rhodomyrtus tomentosa leaves. Rom shows high antibacterial activity against a wide range of Gram-positive bacteria, however, its mode of action is still unclear. Reporter gene assays and proteomic profiling experiments in Bacillus subtilis indicate that Rom does not address classical antibiotic targets like translation, transcription or DNA replication, but acts at the cytoplasmic membrane. In Staphylococcus aureus, Rom decreases the membrane potential within seconds and at low doses, causes release of ATP and even the excretion of cytoplasmic proteins (ECP), but does not induce pore-formation as for example nisin. Lipid staining revealed that Rom induces local membrane damage. Rom's antimicrobial activity can be antagonized in the presence of a very narrow spectrum of saturated fatty acids (C15:0, C16:0, or C18:0) that most likely contribute to counteract the membrane damage. Gram-negative bacteria are resistant to Rom, presumably due to reduced penetration through the outer membrane and its neutralization by LPS. Rom is cytotoxic for many eukaryotic cells and studies with human erythrocytes showed that Rom induces eryptosis accompanied by erythrocyte shrinkage, cell membrane blebbing, and membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Rom's distinctive interaction with the cytoplasmic membrane reminds on the amphipathic, alpha-helical peptides, the phenol-soluble modulins (PSMs), and renders Rom an important tool for the investigation of membrane physiology. [Display omitted] •Rom (rhodomyrtone) is a plant-derived acylphloroglucinol isolated from Rhodomyrtus tomentosa leaves.•In bacterial membranes Rom uncouples the membrane potential and causes release of ATP, lipids and cytoplasmic proteins.•Saturated fatty acids and LPS abrogate Rom's antimicrobial activity.•In erythrocytes Rom causes eryptosis and phosphatidylserine translocation in the plasma membrane.