Low-Molecular-Weight Polylysines with Excellent Antibacterial Properties and Low Hemolysis

The steady development of bacterial resistance has become a global public health issue, and new antibacterial agents that are active against drug-resistant bacteria and less susceptible to bacterial resistance are urgently needed. Here, a series of low-molecular-weight cationic polylysines (C-x-PLLn) with different hydrophobic end groups (C-x) and degrees of polymerization (PLLn) was synthesized and used in antibacterial applications. All the obtained C-x-PLLn have antibacterial activity. Among them, C6-PLL13 displays the best antibacterial effect for Gram-positive bacteria, that is, Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA), and highest selectivity against Gram-positive bacteria. A mechanistic study revealed that the C-6-PLL13 destroys the integrity of the bacterial cell membrane and causes effective bacterial death. Owing to this membrane-disrupting property, C-6-PLL13 showed rapid bacterial killing kinetics and was not likely to develop resistance after repeat treatment (up to 13 generations). Moreover, C-6-PLL13 demonstrated a significant therapeutic effect on an MRSA infection mouse model, which further proved that this synthetic polymer could be used as an effective weapon against bacterial infections.

Automated summary

The development of bacterial resistance is a global health issue. This study synthesized low-molecular-weight cationic polylysines and found that C6-PLL13 exhibited excellent antibacterial activity against Gram-positive bacteria, particularly Staphylococcus aureus and methicillin-resistant Staphylococcus aureus. It was mechanistically revealed that C-6-PLL13 destroyed the integrity of bacterial cell membranes, causing effective bacterial death. Furthermore, C-6-PLL13 showed significant therapeutic effects in an MRSA infection mouse model.