Synergistic Effect of Propidium Iodide and Small Molecule Antibiotics with the Antimicrobial Peptide Dendrimer G3KL against Gram-Negative Bacteria

被引:20
作者
Gan, Bee-Ha [1 ]
Cai, Xingguang [1 ]
Javor, Sacha [1 ]
Kohler, Thilo [2 ,3 ]
Reymond, Jean-Louis [1 ]
机构
[1] Univ Bern, Dept Chem & Biochem, Freiestr 3, CH-3012 Bern, Switzerland
[2] Univ Geneva, Dept Microbiol & Mol Med, CH-1211 Geneva, Switzerland
[3] Geneva Univ Hosp, Infect Dis Serv, CH-1211 Geneva, Switzerland
基金
瑞士国家科学基金会;
关键词
antimicrobial peptides; dendrimers; membrane permeabilization; antibiotics; synergy;
D O I
10.3390/molecules25235643
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页数:12
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