Rooney Lorcan J P, Marshall Andrew, Tunney Michael M, Tabaei Seyed R
School of Chemistry and Chemical Engineering, Queen's University Belfast, David Keir Building, Stranmillis Road, Belfast BT9 5AG, U.K.
School of Pharmacy, Queen's University Belfast, Medical Biology Centre, Lisburn Road, Belfast BT9 7BL, U.K.
ACS Appl Mater Interfaces. 2025 Apr 2;17(13):19276-19285. doi: 10.1021/acsami.4c20874. Epub 2025 Mar 18.
Bacterial biofilms present significant therapeutic challenges due to their resistance to conventional antimicrobial treatment. Mucins typically serve as a protective barrier against pathogens, yet certain bacteria, such as (), can exploit these glycoproteins as attachment sites for biofilm formation. This study introduces boronic acid-functionalized polyethyleneimine (PEI-BA) as a promising antibiofilm agent that effectively blocks bacterial adhesion to mucin-rich surfaces. Through the multivalent presentation of boronic acid groups, PEI-BA reversibly forms boronate ester bonds with mucin glycans, creating a protective barrier. Our findings show that PEI-BA prevents bacterial attachment through a nonbactericidal mechanism, potentially reducing the risk of resistance development. Notably, PEI-BA synergizes with a conventional antibiotic, tobramycin, significantly enhancing biofilm inhibition compared to either treatment alone. Systematic evaluation of PEI-BA formulations identified optimal functionalization levels, balancing glycan-binding capability with solubility. From a biomaterials design perspective, we demonstrate how rational polymer modification can transform a potent but cytotoxic antimicrobial agent (i.e., PEI) into a safe and effective antibiofilm material, opening further possibilities for managing biofilm-associated infections in clinical settings. This work establishes boronic acid-based nanomaterials as promising candidates for biofilm prevention and antibiotic enhancement, particularly in conditions like cystic fibrosis, where mucin-bacterial interactions contribute to disease progression.
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