Role of Toxins in Lung Infections Caused by Pseudomonas Aeruginosa

The goal of this study is to determine whether virulence determinants that use the type
III-secretory pathway may be important in the pathogenesis of chronic Pseudomonas aeruginosa
lung infections in patients with cystic fibrosis (CF). The studies will quantify bacterial
effector proteins in serum and sputum and the immune response to specific products as
reflected by antibodies in serum. Candidate effector proteins include: (1) exotoxin A, a
non-type III-dependent ADP-ribosyltransferase and cytotoxin that does not use the Type III
secretory pathway, (2) ExoS, a type III pathway-dependent extracellular
ADP-ribosyltransferase with cytotoxic activity, (3) ExoU, another type III-dependent
cytotoxin, that is responsible for epithelial injury in acute lung infections, and (4) PcrV,
a homolog to the V antigen of Yersinia.

- INCLUSION CRITERIA:

Patients with cystic fibrosis with a defined mutation in the cystic fibrosis transmembrane
regulator (CFTR) (e.g., any of the known variants of the CFTR gene, such as the delta F508
allele).

Patients will have been tested or will be tested for the CFTR gene under another protocol.

Research volunteers that are age-and race-matched as control subjects.

EXCLUSION CRITERIA:

Patients who are less than 9 years of age. Research volunteers less than 18 years of age.

Patients or research volunteers who test positive for human immunodeficiency virus (HIV) or
a positive serum test for hepatitis B and/or C virus.

Patients or research volunteers who test positive for tuberculosis.

Research volunteers with pulmonary disease or infection.