Synthetic Star Nanoengineered Antimicrobial Polymers as Antibiofilm Agents: Bacterial Membrane Disruption and Cell Aggregation

Antimicrobial resistance has become a worldwide issue,with multiresistantbacterial strains emerging at an alarming rate. Multivalent antimicrobialpolymer architectures such as bottle brush or star polymers have showngreat potential, as they could lead to enhanced binding and interactionwith the bacterial cell membrane. In this study, a library of amphiphilicstar copolymers and their linear copolymer equivalents, based on acrylamidemonomers, were synthesized via RAFT polymerization. Their monomerdistribution and molecular weight were varied. Subsequently, theirantimicrobial activity toward a Gram-negative bacterium (Pseudomonas aeruginosa PA14) and a Gram-positivebacterium (Staphylococcus aureus USA300)and their hemocompatibility were investigated. The statistical starcopolymer, S-SP25, showed an improved antimicrobial activity comparedto its linear equivalent againstP. aeruginosaPA14. The star architecture enhanced its antimicrobial activity,causing bacterial cell aggregation, as revealed via electron microscopy.However, it also induced increased red blood cell aggregation comparedto its linear equivalents. Changing/shifting the position of the cationicblock to the core of the structure prevents the cell aggregation effectwhile maintaining a potent antimicrobial activity for the smalleststar copolymer. Finally, this compound showed antibiofilm propertiesagainst a robust in vitro biofilm model.

Automated summary

Antimicrobial resistance is a global issue, and the emergence of multiresistant bacterial strains is alarming. Multivalent antimicrobial polymer architectures, such as bottle brush or star polymers, have shown great potential in enhancing interactions with bacterial cell membranes. In this study, amphiphilic star copolymers and their linear equivalents were synthesized and tested for their antimicrobial activity and hemocompatibility. The star copolymer S-SP25 exhibited improved antimicrobial activity against P. aeruginosa PA14 compared to its linear counterpart, although it also induced increased red blood cell aggregation. Shifting the position of the cationic block in the structure prevented cell aggregation while maintaining strong antimicrobial activity for the smallest star copolymer. Additionally, this compound showed antibiofilm properties against in vitro biofilm models.