C-Terminally Engineered Nucleopeptide Based Soft Materials Exhibiting Antibacterial and Antifungal Efficacy against Drug Resistant Strains

Abstract

We report a series of self-assembled thymine-conjugated nucleopeptides with the modulation of C-terminal fatty acyl chains as potent antibacterial and antifungal properties showing non-significant cytotoxicity to human cells. These thymine-conjugated nucleopeptides were designed, synthesized and self-assembled in milli-Q water (pH – 6.9). Field emission gun-Transmission electron microscopic (FEG-TEM) data corroborated that these self-assembled nucleopeptides form nanofibers in milli-Q water. Further, these self-assembled nucleopeptides are found to be potent antibacterial and antifungal scaffolds against multi-drug resistant clinically isolated bacterial and fungal strains. Detailed mechanistic studies revealed that these self-assembled nucleopeptides can permeabilize the both bacterial and fungal membranes, thereby can disintegrate the membrane integrity and generate reactive oxygen species (ROS) which finally causes the microbial cellular lysis and eventually the death of the microbial cells. Noteworthily, MTT cytotoxicity assay (Using HEK-293 cells) and haemolytic assay (using human blood samples) revealed that these nucleopeptides have non-significant cytotoxicity to human cells and thus these can be used as potent antimicrobial therapeutics to combat the emerging threat of antimicrobial resistance. Interestingly, this report vividly established the comparative efficacy of self-assembled nucleopeptides as potent antibacterial and antifungal scaffolds with non-significant cytotoxicity to human cells. Thus this study convincingly demonstrates a distinct structure–function correlation, establishing a rational framework for designing next-generation antimicrobial therapeutics.