In silico-designed antimicrobial peptide targeting MRSA and E. coli with antibacterial and antibiofilm actions

Abstract

Abstract Antibiotic resistance is a paramount global health issue, with numerous bacterial strains continually fortifying their resistance against diverse antibiotics. This surge in resistance levels primarily stems from the overuse and misuse of antibiotics in human, animal, and environmental contexts. In this study, we advocate for exploring alternative molecules exhibiting antibacterial properties to counteract the escalating antibiotic resistance. We identified a synthetic antimicrobial peptide (AMP) by using computational search in AMP public databases and further engineering through molecular docking and dynamics. Microbiological evaluation, cytotoxicity, genotoycity, and hemolysis experiments were then performed. The designed AMP underwent rigorous testing for antibacterial and antibiofilm activities against Methicillin-Resistant Staphylococcus aureus (MRSA) and Escherichia coli (E. coli), representing gram-positive and gram-negative bacteria, respectively. Subsequently, the safety profile of the AMP was assessed in vitro using human fibroblast cells and a human blood sample. The selected AMP demonstrated robust antibacterial and antibiofilm efficacy against MRSA and E. coli, with an added assurance of non-cytotoxicity and non-genotoxicity towards human fibroblasts. Also, the AMP did not demonstrate any hemolytic activity. Our findings emphasize the considerable promise of the AMP as a viable alternative antibacterial agent, showcasing its potential to combat antibiotic resistance effectively.