High-speed atomic force microscopy highlights new molecular mechanism of daptomycin action

Nat Commun. 2020 Dec 9;11(1):6312. doi: 10.1038/s41467-020-19710-z.


The increase in speed of the high-speed atomic force microscopy (HS-AFM) compared to that of the conventional AFM made possible the first-ever visualisation at the molecular-level of the activity of an antimicrobial peptide on a membrane. We investigated the medically prescribed but poorly understood lipopeptide Daptomycin under infection-like conditions (37 °C, bacterial lipid composition and antibiotic concentrations). We confirmed so far hypothetical models: Dap oligomerization and the existence of half pores. Moreover, we detected unknown molecular mechanisms: new mechanisms to form toroidal pores or to resist Dap action, and to unprecedently quantify the energy profile of interacting oligomers. Finally, the biological and medical relevance of the findings was ensured by a multi-scale multi-nativeness-from the molecule to the cell-correlation of molecular-level information from living bacteria (Bacillus subtilis strains) to liquid-suspended vesicles and supported-membranes using electron and optical microscopies and the lipid tension probe FliptR, where we found that the cells with a healthier state of their cell wall show smaller membrane deformations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacillus subtilis / cytology
  • Bacillus subtilis / drug effects*
  • Bacillus subtilis / ultrastructure
  • Bacterial Infections / drug therapy*
  • Bacterial Outer Membrane / drug effects
  • Bacterial Outer Membrane / ultrastructure
  • Cell Wall / drug effects
  • Cell Wall / ultrastructure
  • Daptomycin / pharmacology*
  • Daptomycin / therapeutic use
  • Drug Resistance, Bacterial
  • Humans
  • Lipid Bilayers
  • Microbial Sensitivity Tests
  • Microscopy, Atomic Force*
  • Microscopy, Electron, Transmission
  • Models, Biological


  • Anti-Bacterial Agents
  • Lipid Bilayers
  • Daptomycin