A potent antibacterial effect of short D-enantiomeric peptides

Abstract

The need for antibiotics to effectively treat multi-resistant bacterial infections is emerging as many casualties are predicted by multi-resistant bacteria caused by misuse and abuse of existing antibiotics. Antimicrobial peptides(AMPs) have a wide spectrum of antimicrobial activity and have various mechanisms of action, so AMP has been studied as antibiotics that have the potential to overcome the multi-resistant bacteria problem. In this study, the antibacterial activity of KSH20 and KSH43 designed in the previous study is measured. The KSH series consists of D-form amino acids and is an antibacterial peptide that has improved stability and has enhanced bacterial selectivity by including the amide C terminus. It is confirmed that KSH20 showed high activity even in the presence of human serum against Acinetobacter baumannii and resistant strains, and Klebsiella pneumonia. In the case of KSH43, it is confirmed that it showed a broad antibacterial spectrum targeting ESKAPE pathogen. In addition, the mechanism of action of KSH20 was analyzed through killing kinetics assay and membrane potential change, and it is found that it did destroy the bacterial outer membrane. After verification of the in vitro antibacterial activity, a neutropenia-induced mouse model with a reduced effect on the body's immune system was introduced to confirm the in vivo efficacy of the two antimicrobial peptides against residual bacteria in the skin. In conclusion, it was confirmed that KSH20 is a therapeutic agent for A.baumannii and K.pneumonia, and KSH43 has potential as a therapeutic agent for S. aureus wound infection.