Mechanism of Action of Oxazoline-Based Antimicrobial Polymers Against Staphylococcus aureus: In Vivo Antimicrobial Activity Evaluation

Antimicrobial-resistant pathogens have reached alarming levels, becoming one of the most pressing global health issues. Hence, new treatments are necessary for the fight against antimicrobial resistance. Synthetic nanoengineered antimicrobial polymers (SNAPs) have emerged as a promising alternative to antimicrobial peptides, overcoming some of their limitations while keeping their key features. Herein, a library of amphiphilic oxazoline-based SNAPs using cationic ring-opening polymerization (CROP) is designed. Amphipathic compounds with 70% cationic content exhibit the highest activity against clinically relevant Staphylococcus aureus isolates, maintaining good biocompatibility in vitro and in vivo. The mechanism of action of the lead compounds against S. aureus is assessed using various microscopy techniques, indicating cell membrane disruption, while the cell wall remains unaffected. Furthermore, a potential interaction of the compounds with bacterial DNA is shown, with possible implications on bacterial division. Finally, one of the compounds exhibits high efficacy in vivo in an insect infection model.

Automated summary

Antimicrobial-resistant pathogens have become a significant global health concern, demanding the development of new treatments. Synthetic nanoengineered antimicrobial polymers (SNAPs) show promise as an alternative to antimicrobial peptides, with high activity against Staphylococcus aureus and good biocompatibility. The lead compounds disrupt the cell membrane of S. aureus, while leaving the cell wall unaffected. In addition, there is a potential interaction of the compounds with bacterial DNA, suggesting implications on bacterial division. Finally, one of the compounds exhibits high efficacy in vivo in an insect infection model.