Cystic fibrosis and pulmonary biofilms

Cystic fibrosis (CF) is an autosomal recessive disorder that involves the cystic fibrosis transmembrane conductance regulator. This protein is an anion channel that transfers chloride and bicarbonate from an intracellular location to an extracellular location. This transfer supports the formation of a normal periciliary fluid layer that is essential for ciliary function and the clearance of particulates from bronchi. Changes in mucociliary function can result in chronic bronchitis and recurrent infections. Studies using micro computed tomography of explanted lungs from CF patients have demonstrated that there is a significant reduction in the number of terminal bronchi and that approximately 50% of these bronchi are obstructed with secretions. These airways become colonized with bacteria, such as Pseudomonas aeruginosa, which can form biofilms, and this results in chronic inflammation and chronic airway damage. Biofilm formation can be predicted when mucoid colonies of pseudomonas grow out on routine bacterial cultures of sputum. Studies on the prognosis of patients with CF have demonstrated that there is lack of clear genotype-phenotype correlation, but one recent longitudinal study did report an association between more severe CFTR genotypes and clinical outcomes. In addition, the degree of pulmonary dysfunction and pseudomonas colonization, especially with drug resistant pseudomonas, predict poor outcomes. Bacteria in biofilms are more resistant to antibiotics, and the structure of biofilms limits host defense responses. Treatment approaches include the use of more than one antibiotic, the addition of inhaled antibiotics, the use of enzymes that degrade biofilms, and the use of small molecules that inhibit community metabolism in biofilms. Key words: cystic fibrosis transmembrane conductance regulator, extracellular secretions, periciliary fluid, Pseudomonas aeruginosa, biofilms