Advanced Materials Department, Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.
Institute for Microbiology and Immunology, Medical Faculty, University of Ljubljana, Zaloška 4, 1000, Ljubljana, Slovenia.
Sci Rep. 2017 Jun 28;7(1):4324. doi: 10.1038/s41598-017-04670-0.
Lantibiotics, bacteria-sourced antimicrobial peptides, are very good candidates for effective and safe food additives. Among them, nisin is already approved by the EU and FDA, and has been used in food preservation for the past 40 years. Now, there is a possibility and strong interest to extend its applicability to biomedicine for designing innovative alternatives to antibiotics. The main obstacle is, however, its naturally narrow spectrum of antimicrobial activity, focused on Gram positive bacteria. Here we demonstrate broadening nisin's spectrum to Gram negative bacteria using a nano-engineering approach. After binding nisin molecules to the surface of gold nano-features, uniformly deposited on spherical carbon templates, we created a nanocomposite with a high density of positively charged groups. Before assembly, none of the components of the nanocomposite showed any activity against bacterial growth, which was changed after assembly in the form of the nanocomposite. For the first time we showed that this type of structure enables interactions capable of disintegrating the wall of Gram negative bacteria. As confirmed by the nisin model, the developed approach opens up new horizons for the use of lantibiotics in designing post-antibiotic drugs.
类细菌素是一种源自细菌的抗菌肽,是非常有前途的高效、安全的食品添加剂。其中,乳链菌肽已被欧盟和 FDA 批准使用,在食品保鲜方面已有 40 年的历史。现在,人们有兴趣并有可能将其应用扩展到生物医学领域,设计对抗生素的创新替代品。然而,其主要障碍是抗菌谱狭窄,仅针对革兰氏阳性菌。在这里,我们通过纳米工程方法证明可以将乳链菌肽的抗菌谱扩大到革兰氏阴性菌。在将乳链菌肽分子结合到均匀沉积在球形碳模板上的金纳米结构表面之后,我们制造了一种具有高密度正电荷基团的纳米复合材料。在组装之前,纳米复合材料的任何成分都没有显示出任何抑制细菌生长的活性,而在组装之后,纳米复合材料就会表现出这种活性。我们首次表明,这种结构能够使革兰氏阴性菌的细胞壁发生相互作用而破裂。通过乳链菌肽模型得到证实,所开发的方法为在设计后抗生素药物时使用类细菌素开辟了新的前景。