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 -PLL n ) with different hydrophobic end groups (C x ) and degrees of polymerization (PLL n ) was synthesized and used in antibacterial applications. All the obtained C x -PLL n have antibacterial activity. Among them, C 6 -PLL 13 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 -PLL 13 destroys the integrity of the bacterial cell membrane and causes effective bacterial death. Owing to this membrane-disrupting property, C 6 -PLL 13 showed rapid bacterial killing kinetics and was not likely to develop resistance after repeat treatment (up to 13 generations). Moreover, C 6 -PLL 13 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.