Fluorination of Polyethylenimines for Augmentation of Antibacterial Potency via Structural Damage and Potential Dissipation of Bacterial Membranes.

ABSTRACT

The rise of drug-resistant bacteria (e.g., methicillin-resistant Staphylococcus aureus, MRSA) has continued, making the ″super-bugs″ a formidable threat to global health. Herein, we synthesize a series of fluoroalkylated polyethylenimines (PEI-F) with different grafting degrees of fluoroalkyls via a simple ring-opening reaction and demonstrate for the first time that fluoroalkylated PEIs are able to exert potent antibacterial activity to Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Among the fluoroalkylated polymers, PEI-F3.0 shows the strongest antibacterial activity, with a minimum inhibitory concentration (MIC) of 64 µg mL-1, against both E. coli and S. aureus. More importantly, we find that PEI-F3.0 is able to kill over 99.8% of S. aureus within 1 min, which is extremely desirable for the treatment of acute and severe bacterial infections that require quick disinfection. We also demonstrate that the fluoroalkylated PEIs are able to kill bacteria via structural damage of the outer membrane (OM) and cytoplasmic membrane (CM), potential dissipation of CM, and generation of intracellular reactive oxygen species (ROS). The in vivo antibacterial test suggests that commercial Vaseline blended with 6.25 wt % of PEI-F3.0 (VL/PEI-F3.0) is able to efficaciously eradicate MRSA infection on a bacterial infected wound model and promote the healing procedure of the wound site. Therefore, the fluoroalkylated PEIs provide a promising strategy to cope with the major challenges of drug-resistant infections.