Antimicrobial peptides with high bioactivity against MDR isolates: Addressing public health concerns

Antimicrobial resistance is a rapidly escalating global health concern, largely driven by the overuse and misuse of antibiotics in agriculture and clinical settings. There is an urgent and currently unmet need for effective therapeutics against multi-drug resistant (MDR) pathogens. Antimicrobial peptides (AMPs) are a diverse class of cationic peptides that have the potential to overcome extant resistance mechanisms. We evaluated the antimicrobial efficacy of 13 structurally distinct antimicrobial peptides against a panel of drug-resistant Escherichia coli strains. Toxicity assays, including hemolysis and cell viability tests, were performed to determine therapeutic indices and assess the clinical potential of those select peptides. Our findings indicate that, relative to susceptible reference strains, the tested AMPs retain robust bioactivity against known MDR isolates, exhibiting only marginal or no decrease in antimicrobial efficacy. Among them, TeRu4 emerged as the lead candidate, with a minimum inhibitory concentration of 0.5 μg/mL and a therapeutic index exceeding 256. This study underscores the potential of AMPs to act as powerful alternatives to traditional antibiotics, offering new possibilities to address public health concerns surrounding drug-resistant bacterial infections.