Biofilms and Cystic Fibrosis

A biofilm is a structured community of bacteria adhered to a surface and embedded in a self-produced extracellular polymeric substance (EPS) comprising polysaccharides, proteins, lipids, and extracellular DNA. When host-associated, biofilms also incorporate host-produced fibrin and mucus. Biofilms are heterogeneous: differential access to nutrients across their depth creates metabolic gradients, with cells in the outer layers actively dividing and cells deeper within existing as slow-growing or dormant "persisters." These persisters tolerate antibiotic concentrations many-fold higher than planktonic (free-living) bacteria and survive treatment, leading to relapsing infection.

Biofilm formation proceeds through: initial reversible attachment to a surface; transition to irreversible attachment via adhesins and EPS production; maturation into a three-dimensional structured community; and dispersal of planktonic cells to colonise new sites. Communication within the biofilm population occurs through quorum sensing — bacteria release and detect small signal molecules (autoinducers) to sense population density, co-ordinating gene expression across the entire community as if it were a single organism.

In cystic fibrosis (CF), dysfunction of the CFTR chloride channel causes defective mucociliary clearance, leading to thick mucus accumulation in the airways. This creates an ideal niche for opportunistic pulmonary infection, most critically with Pseudomonas aeruginosa. Initial P. aeruginosa colonisation in CF is with non-mucoid strains; over time, the bacteria undergo adaptive mutations and transition to a mucoid phenotype characterised by alginate overproduction, embedding the bacteria in a protective biofilm within the mucus layer. Chronic pulmonary infection drives a cycle of repeated neutrophil recruitment, inflammatory cytokine release, neutrophil-derived proteases, and oxidant-mediated tissue damage, causing progressive irreversible lung function decline.

Treatment of biofilm-associated infections in CF requires inhaled antibiotics (e.g., tobramycin, aztreonam) to achieve high local concentrations, systemic antibiotic courses that are longer and at higher doses than for non-biofilm infections, and physical airway clearance techniques. Strict infection control is critical because CF patients can transmit virulent P. aeruginosa strains to one another.