The recent rise of multidrug resistant microbial strains requires development of new and novel therapeutic alternatives. In this study, we present a novel antibacterial system that comprises of modified naturally abundant antimicrobial peptides in conjugation with silver nanoparticles. Further, we propose a simple route to incorporate a cysteine residue either at the N- or C-terminal of the parent peptide. Tagging a cysteine residue at the terminals not only enhances the binding propensity of the resultant peptide with the silver nanoparticle, but also increases its antimicrobial property against several pathogenic bacterial strains including K. pneumoniae. The minimum inhibitory concentration (MIC) values of the cysteine tagged nanoconjugates were obtained in the range of 5–15 μM compared to 50 μM for peptides devoid of the cysteines. The origin and mechanism of such improved activity of the conjugates were investigated using NMR spectroscopy and molecular dynamics (MD) simulations. The application of ¹³C-isotope labelled media to track the metabolic lifecycle of E. coli cells provided further insights into the system. MD simulations showed that pore formation in membrane bilayer is mediated through a hydrophobic collapse mechanism. The design strategy described herein opens up new-avenues for using biocompatible nanomedicines as a potential alternative to conventional antibiotics.

近来多药耐药性微生物菌株的兴起要求开发新的和新颖的治疗选择。在这项研究中，我们提出了一种新型的抗菌系统，该系统包含修饰的天然丰富的抗菌肽，并与银纳米颗粒结合在一起。此外，我们提出了在母体肽的N端或C端掺入半胱氨酸残基的简单途径。在末端标记半胱氨酸残基不仅增强了所得肽与银纳米颗粒的结合倾向，而且还提高了其对包括肺炎克雷伯氏菌在内的几种致病细菌菌株的抗菌性能。。半胱氨酸标记的纳米缀合物的最小抑菌浓度（MIC）值在5–15μM范围内，而不含半胱氨酸的肽的抑菌浓度为50μM。使用NMR光谱法和分子动力学（MD）模拟研究了缀合物活性提高的起源和机理。应用¹³ C同位素标记的介质跟踪大肠杆菌细胞的代谢生命周期为系统提供了进一步的见解。MD模拟表明，膜双层中的孔形成是通过疏水性塌陷机制介导的。本文所述的设计策略开辟了使用生物相容性纳米药物作为常规抗生素的潜在替代品的新途径。