Impact of mutant cystic fibrosis transmembrane conductance regulator (CFTR) on cellular physiology. Mutant CFTR promotes initial bacterial infection by upregulating epithelial cell adhesion molecules for bacteria such as asialo-GM1 and by decreasing production of innate host defense molecules such as nitric oxide (NO). Defects in CFTR also lead to increased sodium absorption through the epithelial sodium channel (ENaC) and decreased chloride secretion. Water follows its concentration gradient and results in decreased depth of airway surface liquid. Bacterial persistence is promoted by alterations in airway wall architecture, impaired host defense mechanisms, an excessive inflammatory response, and adaptations made by the bacteria to the microenvironment of the cystic fibrosis airway.