Department of Chemistry and Biochemistry, University of Bern, Freiestrasse 3, 3012 Bern, Switzerland.
Department of Microbiology and Molecular Medicine, University of Geneva, 1211 Geneva, Switzerland.
Molecules. 2020 Nov 30;25(23):5643. doi: 10.3390/molecules25235643.
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 , 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 by , initially detected using the DNA-binding fluorogenic dye propidium iodide (), also leads to a synergistic effect between and in this bacterium. We also identify a synergistic effect between and six different antibiotics against the Gram-negative , against which is inactive.
目前迫切需要开发针对多药耐药菌的新型抗生素。许多抗菌肽 (AMPs) 对这些细菌具有活性，通常通过破坏细胞膜来发挥作用，这种机制也可用于使细菌对其他抗生素具有渗透性，从而产生协同作用。我们最近表明，一种具有肽链多分支树突状拓扑结构的 AMP 可使革兰氏阴性菌的内外膜通透性增加，包括多药耐药菌株，从而有效杀死细菌。在这里，我们表明，最初使用与 DNA 结合的荧光染料碘化丙啶 (PI) 检测到的 ，可使 对革兰氏阴性菌的内外膜通透性增加，这也导致了该细菌中 与 的协同作用。我们还发现 与针对革兰氏阴性 的六种不同抗生素之间存在协同作用，而 对 无效。
