Development and Evaluation of the Efficacy and Toxicity of a New Hybrid Antimicrobial Peptide MY8

Abstract

Background:: Antibiotics have led to significant advancements in medicine. Unfortunately, they were faced with the emergence of pathogen resistance. According to the World Health Organization, antimicrobial resistance has been declared one of humanity's top ten global public health threats. The risk of those bacteria is not only from their being resistant to multi-antibiotics but also from their ability to form biofilms, which can be 1,000 times more resistant than planktonic bacteria. Method:: This study used rational design to hybridize two antimicrobial peptides, aiming to enhance their efficacy and stability with reduced toxicity. Results:: The MY8 novel peptide was designed from the parent peptides BMAP-27 and CAMP 211-225. Some amino acid modifications were introduced to the hybrid peptide to improve its physicochemical properties guided by several software. Its antimicrobial activity has been studied against gram-negative and gram-positive strains, which showed broad-spectrum activity with MIC values against planktonic bacteria ranging from 0.125 to 25 μM. In contrast, 25-200 μM were needed to eradicate biofilms. Moreover, the MY8 peptide showed synergism with four conventional antibiotics., It also showed reduced toxicity against mammalian cells and a slight hemolysis tendency towards erythrocytes. Conclusion:: The design of the MY8 peptide was successful, resulting in a novel, potent, broad-spectrum antimicrobial peptide with reduced toxicity and possible synergism with conventional antibiotics.