Bacterial infections caused of multidrug resistance pathogens are predicted to cause more than 10 million deaths by 2050. Discovery of new antibiotic drugs is of imminent global necessity. Recently, antimicrobial peptides (AMPs) have shown promising antimicrobial activity against a broad range of pathogens. However, only a few have reached clinical trials due their cytotoxicity and highly cost production. Herein, we aimed to mimic and improve the limitations of AMPs by using polymer chemistry. We designed a family of cationic polymers synthetized by reversible addition-fragmentation chain transfer (RAFT) polymerization. The family of polymers differs from each other in their molecular weight and the segregation of the cationic content along the backbone. None of the synthetized polymers showed hemolysis against red blood cells. Additionally, low molecular weight polymers did not show toxicity against fibroblast cells. They showed good antimicrobial activity against S. aureus and P. aeruginosa strains under culture conditions mimicking wound infections and lung infections. Furthermore, the mechanism of action (MOA) of the polymers was investigated against P. aeruginosa strains. The activity of one of the polymers was tested against S. aureus biofilms in a collagen wound model. A complete biofilm inhibition was observed when the artificial wound was pre-treated with the polymer and biofilm eradication was observed in mature biofilms. Cationic polymers offer the possibility to mimic an existing natural product in order to establish a new category of antibiotics with a future scope in clinics.

Cationic antimicrobial polymers: From the mechanism of action to the application against biofilm infection

ACS Fall 2021

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