Fig. 4: Teixobactin–membrane interaction.
From: Teixobactin kills bacteria by a two-pronged attack on the cell envelope
a, High-resolution ssNMR structure of the teixobactin–lipid II complex. b, Zoomed in view of the complex interface. The backbone amino-protons of the depsi-cycle of teixobactin, the End10 sidechain and the N terminus of an adjacent teixobactin coordinate the lipid II PPi group. In addition, End10 interacts with the MurNAc sugar via hydrogen bonds. Blue spheres represent backbone nitrogens; numbers indicate the residue numbers. c, Membrane topology: lipophilic and hydrophilic residues are sharply separated. d, Oligomerization enhances complex stability: molecular dynamics simulations show that inner lipid II molecules (red) are more stably bound than outer molecules (purple). The plot shows the distance between the centre of mass of the PPi group and the centre of mass of amino-protons of the depsi-cycle averaged over the last 200 ns of two molecular dynamics simulations. Source data are provided as a Source Data file. e, Upon lipid II-induced oligomerization, the hydrophobic side of teixobactin faces the membrane surface, which displaces the polar lipid headgroups and concentrates non-lamellar lipid II tails, causing membrane distortions. f,g, Membrane thickness obtained from molecular dynamics simulations, averaged over the last 50 ns. The membrane is thinner at the site of the complex. The red and blue colours show membrane thickness minima and maxima, respectively. h, Bacterial assays with Staphylococcus simulans were used to study membrane depolarization (DiSC; upper panel) and membrane damage (Sytox; lower panel) caused by teixobactin, nisin, plectasin, vancomycin and sans antibiotic. Arrows indicate the addition of antibiotics. Source data are provided as a Source Data file.
