Systematic comparison of activity and mechanism of antimicrobial peptides against nosocomial pathogens

The World Health Organisation has deemed several multi-drug resistant (MDR) nosocomial bacterial pathogens to be of significant threat to human health. A stark increase in morbidity, mortality and the burden to healthcare systems around the world can be attributed to the development of resistance in these bacteria. Accordingly, alternative antimicrobial agents have been sought as an attractive means to combat MDR pathogens, with one such example being antimicrobial peptides (AMPs). Given the reported activity of AMPs, including Pardaxin, MSI-78, dermaseptin-PC (DMPC) and Cecropin B, it is important to understand their activities and modes of action against bacteria for further AMP design. In this study, we compared these AMPs against a panel of nosocomial bacterial pathogens, followed by detailed mecha-nistic studies. It was found that Pardaxin (1-22) and MSI-78 (4-20) displayed the most pronounced antimicrobial activity against the tested bacteria. The mechanistic studies by membrane permeability and molecular dynamics simulation further confirmed the strong membrane interaction and structure of Pardaxin (1-22) and MSI-78 (4-20), which contributed to their potent activity. This study demonstrated a structure and activity guidance for further design of Pardaxin (1-22) and MSI-78 (4-20) as thera-peutics against MDR pathogens. The different effects of DMPC (1-19) and Cecropin B (1-21) on mem-brane integrity and phospholipid membrane interactions provided critical information for the rational design of next-generation analogues with specificity against either Gram-negative or Gram-positive bacteria.(c) 2022 Elsevier Masson SAS. All rights reserved.

Automated summary

The World Health Organisation has identified several multi-drug resistant nosocomial bacterial pathogens as a significant threat to human health. This study compares the antimicrobial activities of different antimicrobial peptides (AMPs) against these pathogens and investigates their modes of action. Pardaxin and MSI-78 show the most pronounced antimicrobial activity and their strong membrane interaction and structure contribute to their potency. The study provides guidance for the design of therapeutics against multi-drug resistant pathogens.