The Design and Functional Characterization of the Antimicrobial and Antibiofilm Activities of BMAP27-Melittin, a Rationally Designed Hybrid Peptide

Abstract

BMAP-27 and melittin are two antimicrobial peptides (AMPs) that display potent antimicrobial activities against a wide range of microbes including multidrug resistant (MDR) strains of bacteria. Unfortunately, their significant toxicity against eukaryotic cells has hampered their development into clinically useful antibiotics. In this study, we have rationally designed a novel hybrid AMP aiming to retain the potent antimicrobial activities of BMAP-27 and melittin while enhancing their therapeutic index. The strategy employed in our design was based on combining the activities of individual α-helical fragments of each AMP to generate a novel hybrid AMP with improved characteristics compared to the parent peptides. Named as BMAP27-Melittin, the novel peptide displayed broad spectrum antimicrobial activity against standard representative Gram-positive and Gram-negative bacterial strains in the range of 1–7.5 µM. Moreover, the peptide managed to kill standard resistant strains of MDR bacteria with significant potency and with MIC values as low as 1 µM. BMAP27-Melittin also proved to exhibit potent antibiofilm activities while the hemolytic and antiproliferative studies against eukaryotic cells revealed that the peptide is exhibiting minimal toxicity at antimicrobial concentrations. Additionally, the molecular dynamics simulations of the peptide folding displayed that the hybrid peptide has folded into a well-defined α-helical structure; supporting the experimental findings. Overall, this work highlights the potential of rational design in generating improved AMPs with enhanced specificity that could be developed into successful therapeutics for the treatment of bacterial infections.