Bactericidal activity of amphipathic cationic antimicrobial peptides involves altering the membrane fluidity when interacting with the phospholipid bilayer

Soraya Omardien, Jan W. Drijfhout, Frédéric M. Vaz, Michaela Wenzel, Leendert W. Hamoen, Sebastian A.J. Zaat, Stanley Brul*

*Corresponding author for this work

Research output: Contribution to JournalArticleAcademicpeer-review


Background: Amphipathic cationic antimicrobial peptides (AMPs) TC19 and TC84, derived from the major AMPs of human blood platelets, thrombocidins, and Bactericidal Peptide 2 (BP2), a synthetic designer peptide showed to perturb the membrane of Bacillus subtilis. We aimed to determine the means by which the three AMPs cause membrane perturbation in vivo using B. subtilis and to evaluate whether the membrane alterations are dependent on the phospholipid composition of the membrane. Methods: Physiological analysis was employed using Alexa Fluor 488 labelled TC84, various fluorescence dyes, fluorescent microscopy techniques and structured illumination microscopy. Results: TC19, TC84 and BP2 created extensive fluidity domains in the membrane that are permeable, thus facilitating the entering of the peptides and the leakage of the cytosol. The direct interaction of the peptides with the bilayer create the fluid domains. The changes caused in the packing of the phospholipids lead to the delocalization of membrane bound proteins, thus contributing to the cell's destruction. The changes made to the membrane appeared to be not dependent on the composition of the phospholipid bilayer. Conclusions: The distortion caused to the fluidity of the membrane by the AMPs is sufficient to facilitate the entering of the peptides and leakage of the cytosol. General significance: Here we show in vivo that cationic AMPs cause “membrane leaks” at the site of membrane insertion by altering the organization and fluidity of the membrane. Our findings thus contribute to the understanding of the membrane perturbation characteristic of cationic AMPs.

Original languageEnglish
Pages (from-to)2404-2415
Number of pages12
JournalBiochimica et Biophysica Acta - Biomembranes
Issue number11
Publication statusPublished - Nov 2018
Externally publishedYes


The authors acknowledge Edward A. de Koning and Terrens N.V. Saaki for constructing the strains EKB154 and TNVS205, and Kate Feller for contributing to Fig. 6 during her Bachelor's internship. S. Omardien acknowledges the Erasmus Mundus Action 2 program ( EMA2 ) and University of Amsterdam for funding. S.A.J. Zaat is supported by the FP7-HEALTH -2011 grant 278890 , BALI – Biofilm Alliance. The authors declare that they have no conflict of interest.

FundersFunder number
Seventh Framework Programme278890
FP7 Health
Universiteit van AmsterdamEMA2


    • Amphipathic cationic antimicrobial peptides
    • Bacillus subtilis
    • Essential membrane proteins
    • Membrane fluidity


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