ACS Applied Materials & Interfaces, Journal Year: 2025, Volume and Issue: unknown

Published: April 16, 2025

The fast emergence of bacteria resistance has already threatened global health, and immediate action is required before the another pandemic. Despite substantial progress in chemical synthesis novel antimicrobial compounds advancements understanding resistance, there been only a handful new antibiotics coming to market. Structurally Nanoengineered Antimicrobial Peptide Polymers (SNAPP-stars) are class antimicrobials. Here, we show that lipidation lysine-valine 16-armed SNAPP-star, S16 (lipo-SNAPP-star) where N-terminal arms conjugated with different fatty acids (caproic, C6, lauric, C12, stearic acid, C18) enhanced activity toward S. aureus MRSA. Lipidation by targeting SNAPP-stars bacterial surface binding peptidoglycan, leading greater inner membrane disruption depolarization. Lipo-SNAPP-stars killed under minute, whereas vancomycin took >16 h. were found preferentially target kill MRSA rather than mixed model. Lipid chain length affected activity, C6-S16 having compared C12-S16 > C18-S16. Lauric acid SNAPP-star depolarization but impeded SNAPP-stars' ability transit through peptidoglycan layer disrupt membrane. Microbial flow cytometry showed aided via lipoteichoic specifically peptidoglycan. Further, lipid C18-S16 = S16, which contrasts order ≫ Our data demonstrate enhances an increasing reduces retaining outer layer. did not increase cytotoxicity, improved therapeutic index S16. how its resulting highly biocompatible targets kills "superbug" within minutes.

Language: Английский