Umerska Anita, Cassisa Viviane, Bastiat Guillaume, Matougui Nada, Nehme Hassan, Manero Florence, Eveillard Matthieu, Saulnier Patrick
MINT, UNIV Angers, INSERM 1066, CNRS 6021, Université Bretagne Loire, Angers, Cedex, France.
Laboratoire de bactériologie, CHU Angers, France.
Int J Nanomedicine. 2017 Aug 8;12:5687-5699. doi: 10.2147/IJN.S139625. eCollection 2017.
Development of effective antibacterial agents for the treatment of infections caused by Gram-positive bacteria resistant to existing antibiotics, such as methicillin-resistant (MRSA), is an area of intensive research. In this work, the antibacterial efficacy of two antimicrobial peptides derived from plectasin, AP114 and AP138, used alone and in combination with monolaurin-lipid nanocapsules (ML-LNCs) was evaluated. Several interesting findings emerged from the present study. First, ML-LNCs and both plectasin derivatives showed potent activity against all 14 tested strains of , independent of their resistance phenotype. Both peptides displayed a considerable adsorption (33%-62%) onto ML-LNCs without having an important impact on the particle properties such as size. The combinations of peptide with ML-LNC displayed synergistic effect against , as confirmed by two methods: checkerboard and time-kill assays. This synergistic interaction enables a dose reduction and consequently decreases the risk of toxicity and has the potential of minimizing the development of resistance. Together, these results suggest that ML-LNCs loaded with a plectasin derivative may be a very promising drug delivery system for further development as a novel antibacterial agent against , including MRSA.
开发有效的抗菌剂以治疗由耐现有抗生素的革兰氏阳性菌引起的感染,如耐甲氧西林金黄色葡萄球菌(MRSA),是一个深入研究的领域。在这项工作中,评估了两种源自plec tasin的抗菌肽AP114和AP138单独使用以及与月桂酸单甘油酯脂质纳米胶囊(ML-LNCs)联合使用时的抗菌效果。本研究出现了几个有趣的发现。首先,ML-LNCs和两种plec tasin衍生物对所有14株受试金黄色葡萄球菌均显示出强效活性,与其耐药表型无关。两种肽在ML-LNCs上均表现出相当程度的吸附(33%-62%),而对诸如大小等颗粒性质没有重要影响。肽与ML-LNC的组合对金黄色葡萄球菌显示出协同作用,这通过棋盘法和时间杀菌试验两种方法得到证实。这种协同相互作用能够降低剂量,从而降低毒性风险,并有可能使耐药性的产生最小化。总之,这些结果表明,负载plec tasin衍生物的ML-LNCs可能是一种非常有前景的药物递送系统,可进一步开发成为一种针对包括MRSA在内的金黄色葡萄球菌的新型抗菌剂。