Chronic Pseudomonas aeruginosa infection in cystic fibrosis airway disease: metabolic changes that unravel novel drug targets

The cystic fibrosis (CF) airways have an incompletely characterized defect in innate defense that eventually leads to bacterial infection and airway inflammation. Persistent Pseudomonas aerugionsa infection resulting from defective innate immunity and a bacterial phenotypic switch to a more intractable mucoid form inside the airway are now well established as important components of CF pathogenesis. Broad-based factors leading to chronic infection will be discussed with respect to: bacterial virulence in the context of biofilm formation, quorum sensing machinery and alginate overproduction, and failure of innate lung immunity in CF airways. In addition, a controversial question as to whether inflammation or infection comes first during CF airway disease will be addressed. Finally, a new hypothesis, that P. aeruginosa thrives as biofilms within the thickened anaerobic mucus layers, will be developed.ope