A. Computed tomography scans of a healthy left lung; and the left lung of CF patient 1 showing characteristic severe disease in the upper, and mild disease in the lower lobes. B. Growth over time in media containing indicated carbon and nitrogen sources, as measured by phenotype microarrays (red=upper lobe isolate, green=lower lobe isolate, yellow=overlap; see ). C. Ciprofloxacin MIC of the lower lobe, upper lobe, and upper lobe isolate with a corrected parE gene (see ). D-F. The upper lobe isolate is compared to the lower lobe isolate, or the upper lobe isolate in which wild type exsD is restored. Results are representative of 3 or more experiments. D. Cytotoxicity to A549 epithelial cells as measured by LDH release, relative to detergent-treated cells (set at 100%). Also included are PAK (positive control), the PAK exsA mutant (negative control), and the left lower lobe isolate with exsD T188P (mean +/− SEM). E. Mouse mortality following intratracheal infection (upper lobe isolate, circle; lower lobe isolate, square; upper lobe isolate with wild type exsD restored, diamond). F. Bacterial survival after exposure to human neutrophils (upper lobe isolate, circle; lower lobe isolate, square; upper lobe isolate with wild type exsD restored, diamond). G. Bacterial survival after treatment with human serum. H. Macrophage IL-1β release after exposure to bacteria (C-H, *P<0.05, paired Student’s t-test).