The novel antibiotic rhodomyrtone traps membrane proteins in vesicles with increased fluidity

• DOI: 10.1371/journal.ppat.1006876
• Publication Date: 2018-02-16T18:32:40Z
• Authors: Dennapa Saeloh; Varomyalin Tipmanee; Kin Ki Jim; Marien P. Dekker; Wilbert Bitter; Supayang P. Vorav...; Michaela Wenzel; Leendert W. Hamoen
• Keywords: Membrane Curvature; Cell membrane

The acylphloroglucinol rhodomyrtone is a promising new antibiotic isolated from the rose myrtle Rhodomyrtus tomentosa, plant used in Asian traditional medicine. While many studies have demonstrated its antibacterial potential variety of clinical applications, very little known about mechanism action rhodomyrtone. Preceding been focused on intracellular targets, but no specific protein could be confirmed as main target. Using live cell, high-resolution, and electron microscopy we demonstrate that causes large membrane invaginations with dramatic increase fluidity, which attract broad range proteins. Invaginations then form vesicles, thereby trapping these Aberrant localization impairs several cellular functions, including respiratory chain ATP synthase complex. Being uncharged devoid particular amphipathic structure, did not seem to typical membrane-inserting molecule. In fact, molecular dynamics simulations showed instead inserting into bilayer, transiently binds phospholipid head groups distortion lipid packing, providing explanations for fluidization induction curvature. Both transient binding mode ability protein-trapping vesicles are unique, making it an attractive candidate novel action.