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

## TL;DR

This review discusses how Pseudomonas aeruginosa biofilms contribute to chronic lung infections in cystic fibrosis and explores new methods and therapies to combat them.

## Contribution

The paper provides a comprehensive overview of biofilm structure, regulation, and interactions in CF, highlighting novel therapeutic strategies.

## Key findings

- Pseudomonas aeruginosa biofilms are central to chronic infection and antibiotic resistance in cystic fibrosis.
- Regulatory mechanisms like c-di-GMP and quorum-sensing systems are crucial for biofilm formation and maintenance.
- Emerging therapies such as matrix-disrupting enzymes and bacteriophage show promise in targeting biofilms.

## 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.