Antimicrobial peptide dendrimers against multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii with enhanced angiogenic effect

Darbre, Tamis (4 September 2016). Antimicrobial peptide dendrimers against multidrug resistant Pseudomonas aeruginosa and Acinetobacter baumannii with enhanced angiogenic effect (Unpublished). In: European Peptide Sympsoium (EPS). Leipzig, Germany. 04.-09.09.2016.

Multi-drug resistant bacteria represent a major public health
threat. In particular, Gram-negative pathogens such as
Pseudomonas aeruginosa are responsible for significant morbidity
and mortality in hospitals, making it urgent to develop
new classes of antimicrobials. Peptide based antimicrobials
offer an attractive opportunity to control these pathogens].
We have developed potent antimicrobial peptides with a
branched structure (peptide dendrimers) with high activity
against multi-resistant clinical isolates of P. aeruginosa and
Acinetobacter baumanii by screening a third generation peptide
dendrimer library. Our best compound G3KL is composed
of natural L-lysine and L-leucine residues (37 amino
acid residues in total) linked by amide bonds but due to the
branched topology it is stable to serum proteases in contrast
to linear peptides to red blood cells and, in contrast to linear
AMPs, stability and high activity in human serum.1 The
activity of G3KL (MIC values) is 4-8 mg/ml for a large panel
of P. aeruginosa and A. baumannii resistant strains.2 The
antimicrobial G3KL showed low toxicity to red blood cells
(MHC of 1000 mg/ml), CHO and epitelial cells. We have
also showed that peptide dendrimers such as G3KL exert direct
potent pro-angiogenic effects and can be incorporated in
biolofical bandage formulation to improve the healing process
in severe burn wounds.3
1. Combining topology and sequence design for the discovery of potent antimicrobial
peptide dendrimers against multidrug-resistant Pseudomonas aeruginosa.
Stach M, Siriwardena T N, Köhler T, van Delden C, Darbre T, Reymond J-L. Angew
Chem Int Ed. 2014, 53, 12827-31.
2. In Vitro Activity of a Novel Antimicrobial Peptide Dendrimer (G3KL) Against
Multidrug-Resistant Acinetobacter baumannii and Pseudomonas
aeruginosa. Pires J, Siriwardena T N, Stach M, Tinguely R, Kasraian S, Luzzaro
F, Leib S L, Darbre T, Reymond J-L, Endimiani A.,. Antimicrob. Agents
Chemother., 2015, 59, 7915-7918.
3. Anti-Microbial Dendrimers against Multidrug-Resistant P. aeruginosa Enhance
the Angiogenic Effect of Biological Burn-wound Bandages. Abdel-Sayed P, Kaeppli
A, Siriwardena T, Darbre T, Perron K, Jafari P, Reymond J-L, Pioletti D P, Applegate
L A, Sci. Rep., 2016, doi:10.1038/srep22020.

Item Type:

Conference or Workshop Item (Speech)

Division/Institute:

08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP)

UniBE Contributor:

Darbre, Tamis

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 540 Chemistry

Language:

English

Submitter:

Sandra Tanja Zbinden Di Biase

Date Deposited:

09 Jun 2017 16:33

Last Modified:

05 Dec 2022 15:02

URI:

https://boris.unibe.ch/id/eprint/95363

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