Violacein Targets the Cytoplasmic Membrane of Bacteria

ACS Infect Dis. 2019 Apr 12;5(4):539-549. doi: 10.1021/acsinfecdis.8b00245. Epub 2019 Feb 12.


Violacein is a tryptophan-derived purple pigment produced by environmental bacteria, which displays multiple biological activities, including strong inhibition of Gram-positive pathogens. Here, we applied a combination of experimental approaches to identify the mechanism by which violacein kills Gram-positive bacteria. Fluorescence microscopy showed that violacein quickly and dramatically permeabilizes B. subtilis and S. aureus cells. Cell permeabilization was accompanied by the appearance of visible discontinuities or rips in the cytoplasmic membrane, but it did not affect the cell wall. Using in vitro experiments, we showed that violacein binds directly to liposomes made with commercial and bacterial phospholipids and perturbs their structure and permeability. Furthermore, molecular dynamics simulations were employed to reveal how violacein inserts itself into lipid bilayers. Thus, our combined results demonstrate that the cytoplasmic membrane is the primary target of violacein in bacteria. The implications of this finding for the development of violacein as a therapeutic agent are discussed.

Keywords: Staphylococcus aureus; daptomycin; mechanism of action; membrane disruption; membrane-active agent; violacein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology*
  • Bacillus subtilis / chemistry
  • Bacillus subtilis / drug effects*
  • Bacillus subtilis / growth & development
  • Cell Membrane / chemistry
  • Cell Membrane / drug effects*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Microbial Sensitivity Tests
  • Molecular Dynamics Simulation
  • Staphylococcus aureus / chemistry
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / growth & development


  • Anti-Bacterial Agents
  • Indoles
  • violacein