Designing Melittin-Graphene Hybrid Complexes for Enhanced Antibacterial Activity

Antimicrobial peptides (AMPs) promise a fundamental solution to the devastating threat of drug-resistant bacteria. However, drawbacks of AMPs (e.g., poor cell membrane penetration efficiency) seriously block their clinical use. In this work, rational design of a hybrid complex of melittin (as a representative AMP) and graphene or graphene oxide (Gra or GO) nanosheets for enhanced antibacterial ability is achieved, via combining in-silico prediction and in-tube test. In comparison to pristine melittin, the specifically designed AMP-Gra (/GO) complex exhibits remarkable efficiency in transmembrane perforation with an over tenfold decrease in the threshold working concentration of peptide; moreover, it has an up to 20-fold enhancement in antibacterial activity against both Gram-negative and Gram-positive bacteria. Such improvement is ascribed to the synergetic insertion of nanosheets and melittin due to similarity in antibacterial mechanism between them and is further regulated by the structural factors of the complex, including the intersheet spacing and surface functionalization of the Gra/GO sheets, etc. These results provide practical guidelines to engineer AMPs with nanotechnology for improved antimicrobial performances, especially based on targeted functionalization of the Gra/GO nanosheets.