Synergistic Effect of Propidium Iodide and Small Molecule Antibiotics with the Antimicrobial Peptide Dendrimer G3KL against Gram-Negative Bacteria |
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| Authors: | Bee-Ha Gan,Xingguang Cai,Sacha Javor,Thilo Kö hler,Jean-Louis Reymond |
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| Affiliation: | 1.Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland; (B.-H.G.); (X.C.); (S.J.);2.Department of Microbiology and Molecular Medicine, University of Geneva, 1211 Geneva, Switzerland;3.Service of Infectious Diseases, Geneva University Hospitals, 1211 Geneva, Switzerland |
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| Abstract: | There is an urgent need to develop new antibiotics against multidrug-resistant bacteria. Many antimicrobial peptides (AMPs) are active against such bacteria and often act by destabilizing membranes, a mechanism that can also be used to permeabilize bacteria to other antibiotics, resulting in synergistic effects. We recently showed that G3KL, an AMP with a multibranched dendritic topology of the peptide chain, permeabilizes the inner and outer membranes of Gram-negative bacteria including multidrug-resistant strains, leading to efficient bacterial killing. Here, we show that permeabilization of the outer and inner membranes of Pseudomonas aeruginosa by G3KL, initially detected using the DNA-binding fluorogenic dye propidium iodide (PI), also leads to a synergistic effect between G3KL and PI in this bacterium. We also identify a synergistic effect between G3KL and six different antibiotics against the Gram-negative Klebsiella pneumoniae, against which G3KL is inactive. |
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| Keywords: | antimicrobial peptides dendrimers membrane permeabilization antibiotics synergy |
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