Extracellular Polymeric Substances of Pseudomonas aeruginosa Biofilms: Roles in Antimicrobial Resistance and Emerging EPS Targeted Disruption Strategies

Pseudomonas aeruginosa is a Gram-negative, aerobic, WHO-designated Critical Priority pathogen due to increasing antimicrobial resistance. It causes healthcare-associated infections in patients with cystic fibrosis, cancer, burns and chronic wounds. Biofilm formation further enhances multidrug resistance and is primarily mediated by Extracellular Polymeric Substances (EPS). This study evaluates the architecture, functions, composition, and disruption strategies of EPS (alginate, Pel, Psl) to provide insight into antibiotic efficacy against them. The EPS acts as a dynamic scaffold that creates diffusion gradients and facilitates immune evasion through inhibition of phagocytosis. It also influences the transfer of antibiotic resistance genes, isolates drugs through steric hindrance and promotes physiological heterogeneity for persister cell formation. Targeting EPS to inhibit biofilms includes strategies such as enzymatic degradation via glycoside hydrolases and alginate lyases, phage-derived depolymerases, and nanomaterials like AgNPs or phage-liposome nanoconjugates. A combination of therapies, incorporating both traditional antibiotics and EPS targeting agents, enhances treatment outcomes. Despite challenges, targeted disruption of EPS using innovative strategies shows a shift from relying solely on antibiotics towards precision-focused biofilm management to tackle P. aeruginosa. This review highlights the central role of EPS in mediating resistance and underscores its potential as a key therapeutic target in P. aeruginosa infections.