Payne Jennifer A E, Kulkarni Ketav, Izore Thierry, Fulcher Alex J, Peleg Anton Y, Aguilar Marie-Isabel, Cryle Max J, Del Borgo Mark P
Infection and Immunity Program, The Monash Biomedicine Discovery Institute, Department of Biochemistry and Molecular Biology, Monash University Clayton Victoria 3800 Australia
EMBL Australia, Monash University Clayton Victoria 3800 Australia.
Nanoscale Adv. 2021 Mar 24;3(9):2607-2616. doi: 10.1039/d0na01018a. eCollection 2021 May 4.
The increasing resistance of pathogenic microbes to antimicrobials and the shortage of antibiotic drug discovery programs threaten the clinical use of antibiotics. This threat calls for the development of new methods for control of drug-resistant microbial pathogens. We have designed, synthesised and characterised an antimicrobial material formed the self-assembly of a population of two distinct β-peptide monomers, a lipidated tri-β-peptide (β-peptide) and a novel β-peptide conjugated to a glycopeptide antibiotic, vancomycin. The combination of these two building blocks resulted in fibrous assemblies with distinctive structures determined by atomic force microscopy and electron microscopy. These fibres inhibited the growth of methicillin resistant (MRSA) and associated directly with the bacteria, acting as a peptide nanonet with fibre nucleation sites on the bacteria observed by electron microscopy and confocal microscopy. Our results provide insights into the design of peptide based supramolecular assemblies with antibacterial activity and establish an innovative strategy to develop self-assembled antimicrobial materials for future biomedical application.
致病微生物对抗菌药物的耐药性不断增强，以及抗生素药物研发项目的短缺，威胁着抗生素的临床应用。这种威胁促使人们开发控制耐药性微生物病原体的新方法。我们设计、合成并表征了一种抗菌材料，该材料由两种不同的β-肽单体自组装而成，一种是脂化三β-肽（β-肽），另一种是与糖肽抗生素万古霉素偶联的新型β-肽。这两种构建模块的组合产生了具有独特结构的纤维状聚集体，通过原子力显微镜和电子显微镜确定了其结构。这些纤维抑制了耐甲氧西林金黄色葡萄球菌（MRSA）的生长，并直接与细菌相关联，通过电子显微镜和共聚焦显微镜观察到，它们在细菌上作为具有纤维成核位点的肽纳米网发挥作用。我们的结果为具有抗菌活性的基于肽的超分子聚集体的设计提供了见解，并建立了一种创新策略，以开发用于未来生物医学应用的自组装抗菌材料。
