Gan, Bee Ha; Siriwardena, Thissa N.; Javor, Sacha; Darbre, Tamis; Reymond, Jean-Louis (2019). Fluorescence Imaging of Bacterial Killing by Antimicrobial Peptide Dendrimer G3KL. ACS infectious diseases, 5(12), pp. 2164-2173. American Chemical Society 10.1021/acsinfecdis.9b00299
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We recently discovered that peptide dendrimers such as G3KL ((KL)8(KKL)4(KKL)2KKL, K = branching l-lysine) exert strong activity against Gram-negative bacteria including Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. Herein, we report a detailed mechanistic study using fluorescence labeled analogs bearing fluorescein (G3KL-Fluo) or dansyl (G3KL-Dansyl), which show a similar bioactivity profile as G3KL. Imaging bacterial killing by super-resolution stimulated emission depletion (STED) microscopy, time-lapse imaging, and transmission electron microscopy (TEM) reveals that the dendrimer localizes at the bacterial membrane, induces membrane depolarization and permeabilization, and destroys the outer leaflet and the inner membrane. G3KL accumulates in bacteria against which it is active; however, it only weakly penetrates into eukaryotic cells without inducing significant toxicity. G3KL furthermore binds to lipopolysaccharide (LPS) and inhibits the LPS induced release of TNF-α by macrophages, similarly to polymyxin B. Taken together, these experiments show that G3KL behaves as a potent membrane disruptive antimicrobial peptide.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Gan, Bee Ha, Siriwardena, Thissa Appuhamilage, Javor, Sacha, Darbre, Tamis, Reymond, Jean-Louis |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
2373-8227 |
Publisher: |
American Chemical Society |
Language: |
English |
Submitter: |
Sandra Tanja Zbinden Di Biase |
Date Deposited: |
24 Jan 2020 15:16 |
Last Modified: |
05 Dec 2022 15:35 |
Publisher DOI: |
10.1021/acsinfecdis.9b00299 |
PubMed ID: |
31618574 |
BORIS DOI: |
10.7892/boris.138519 |
URI: |
https://boris.unibe.ch/id/eprint/138519 |
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