Aleksic Ivana, Petkovic Milos, Jovanovic Milos, Milivojevic Dusan, Vasiljevic Branka, Nikodinovic-Runic Jasmina, Senerovic Lidija
Institute of Molecular Genetics and Genetic Engineering, University of Belgrade, Belgrade, Serbia.
Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia.
Front Microbiol. 2017 Dec 8;8:2454. doi: 10.3389/fmicb.2017.02454. eCollection 2017.
A new strain, namely sp. BV152.1 was isolated from the rhizosphere of ground ivy ( L.) producing metabolites with potent ability to inhibit biofilm formation of an important human pathogens PAO1, , and . Structural characterization revealed di-rhamnolipids mixture containing rhamnose (Rha)-Rha-C10-C10, Rha-Rha-C8-C10, and Rha-Rha-C10-C12 in the ratio 7:2:1 as the active principle. Purified di-rhamnolipids, as well as commercially available di-rhamnolipids (Rha-Rha-C10-C10, 93%) were used as the substrate for the chemical derivatization for the first time, yielding three semi-synthetic amide derivatives, benzyl-, piperidine-, and morpholine. A comparative study of the anti-biofilm, antibacterial and cytotoxic properties revealed that di-Rha from sp. BV152.1 were more potent in biofilm inhibition, both cell adhesion and biofilm maturation, than commercial di-rhamnolipids inhibiting 50% of PAO1 biofilm formation at 50 μg mL and 75 μg mL, respectively. None of the di-rhamnolipids exhibited antimicrobial properties at concentrations of up to 500 μg mL. Amide derivatization improved inhibition of biofilm formation and dispersion activities of di-rhamnolipids from both sources, with morpholine derivative being the most active causing more than 80% biofilm inhibition at concentrations 100 μg mL. Semi-synthetic amide derivatives showed increased antibacterial activity against , and also showed higher cytotoxicity. Therefore, described di-rhamnolipids are potent anti-biofilm agents and the described approach can be seen as viable approach in reaching new rhamnolipid based derivatives with tailored biological properties.
从常春藤（Glechoma hederacea L.）根际分离出一种新菌株，即鞘氨醇单胞菌属（Sphingomonas）BV152.1，该菌株产生的代谢产物具有强大的抑制重要人类病原体铜绿假单胞菌（PAO1）生物膜形成的能力。结构表征显示，活性成分是一种二鼠李糖脂混合物，包含鼠李糖（Rha）-Rha-C10-C10、Rha-Rha-C8-C10和Rha-Rha-C10-C12，其比例为7:2:1。纯化的二鼠李糖脂以及市售二鼠李糖脂（Rha-Rha-C10-C10，93%）首次被用作化学衍生化的底物，得到了三种半合成酰胺衍生物，即苄基、哌啶和吗啉衍生物。抗生物膜、抗菌和细胞毒性特性的比较研究表明，鞘氨醇单胞菌属BV152.1的二鼠李糖脂在生物膜抑制方面，无论是细胞黏附还是生物膜成熟，都比市售二鼠李糖脂更有效，市售二鼠李糖脂分别在50 μg/mL和75 μg/mL时抑制50%的PAO1生物膜形成。在高达500 μg/mL的浓度下，所有二鼠李糖脂均未表现出抗菌特性。酰胺衍生化提高了来自两种来源的二鼠李糖脂对生物膜形成的抑制和分散活性，其中吗啉衍生物最具活性，在100 μg/mL浓度下可导致超过80%的生物膜抑制。半合成酰胺衍生物对铜绿假单胞菌显示出增强的抗菌活性，并且还表现出更高的细胞毒性。因此，所述二鼠李糖脂是有效的抗生物膜剂，并且所述方法可被视为获得具有定制生物学特性的新型基于鼠李糖脂的衍生物的可行方法。
