The designing of novel peptide antibiotics to target multi-drug resistance bacteria

Abstract

Since the introduction of penicillin, concerns have escalated due to antibiotic misuse and the relatively limited development of new forms of antibiotics. The emergence of resistance among pathogenic bacteria has heightened the risk of multi-drug resistant (MDR) strains. Recognizing the urgency of antibiotic resistance among major bacterial pathogens, there is a pressing need for the exploration of new antibiotic classes. This study investigates a novel form of antibiotics against Pseudomonas aeruginosa, Acinetobacter baumannii, Enterococcus faecalis, and Staphylococcus aureus. Antimicrobial peptides (AMPs), which are characterized by their amphiphilic and cationic properties, present a potential solution to antibiotic-resistant strains by physically destroying bacterial membranes, unlike conventional antibiotics. The research designs a concise 11-amino acid AMP by integrating positively charged arginine, lysine, and histidine with the hydrophobic amino acid tryptophan and the nonpolar amino acid valine. Acknowledging the sensitivity of AMPs to protease degradation, this design includes D-form amino acids for resistance to proteolytic enzymes. Out of the 13 designed peptides, final candidates HS 5 and HS 7 exhibit robust activity with low toxicity. These candidates evaluated additional testing for killing kinetics, and membrane permeability. It is expected to have potential as a new type of antibiotic that can substitute existing antibiotics.