Pseudomonas aeruginosa Biofilms in Cystic Fibrosis: Interactions, Methods, and Therapeutic Strategies.

Abstract

This review explores the role of Pseudomonas aeruginosa biofilms in cystic fibrosis (CF) pathogenesis. Biofilms, the main bacterial lifestyle in CF lungs, are key in therapy failure, immune evasion, and chronic infection persistence. This review examines biofilm structure, emphasizing extracellular polymeric substances (Psl, Pel, alginate, eDNA) and their roles in structural stability, resistance to antibiotics, and immune modulation. Regulatory mechanisms, including c-di-GMP signaling and quorum-sensing systems, are detailed as key drivers of biofilm formation and maintenance. The review also highlights polymicrobial interactions, particularly with Staphylococcus aureus, Candida spp., and Aspergillus spp., and commensal bacteria, illustrating how interaction dynamics shape microbial behavior, virulence, and treatment outcomes. Methods for studying biofilms in CF-like conditions, such as advanced in vitro models and transcriptomic analyses, are outlined for their relevance in replicating the complex lung environment. Emerging antibiofilm strategies, including matrix-disrupting enzymes, quorum-sensing inhibitors, bacteriophage therapies, and nanomedicine, are discussed as promising tools to combat biofilm resilience. The review underscores the need for innovative therapeutic approaches and a deeper understanding of microbial and host interactions to improve clinical outcomes in CF patients.