Violacein Targets the Cytoplasmic Membrane of Bacteria

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 Gra...

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Bibliographic Details
Published in:ACS infectious diseases 2019-04, Vol.5 (4), p.539-549
Main Authors: Cauz, Ana C. G, Carretero, Gustavo P. B, Saraiva, Greice K. V, Park, Peter, Mortara, Laura, Cuccovia, Iolanda M, Brocchi, Marcelo, Gueiros-Filho, Frederico J
Format: Article
Language:English
Subjects:
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
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Summary: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.
ISSN:2373-8227
2373-8227
DOI:10.1021/acsinfecdis.8b00245