Fluorescence Imaging of Bacterial Killing by Antimicrobial Peptide Dendrimer G3KL

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 > Departement of Chemistry and Biochemistry

UniBE Contributor:

Gan, Bee Ha; Siriwardena, Thissa Appuhamilage; Javor, Sacha; Darbre, Tamis and 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:

17 Oct 2020 02:30

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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