Role of Toxins in Lung Infections Caused by Pseudomonas Aeruginosa
Study Details
Study Description
Brief Summary
Some bacteria that cause disease can produce toxic substances that may worsen the disease. Pseudomonas aeruginosa is a bacteria that can produce a variety of toxins and is of special interest for patients with cystic fibrosis and repeated long term lung infections.
The goal of this study is to determine whether specific toxins produced by Pseudomonas aeruginosa may be important in the disease process of chronic lung infections of patients with cystic fibrosis.
This study will attempt to measure bacterial production of toxins in blood and sputum and immune system response to toxins in the blood....
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Detailed Description
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| 1 Healthy Volunteers |
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| 2 Cystic Fibrosis subjects |
Outcome Measures
Primary Outcome Measures
- Serum will be analyzed for the presence of an immune response, focusing on antibodies against the virulence determinants, whilesputum will be analyzed for the immunological and genetic presence of the virulence determinants. [End of Study]
serum will be analyzed for the presence of an immune response, focusing on antibodies against the virulence determinants, whilesputum will be analyzed for the immunological and genetic presence of the virulence determinants.
Eligibility Criteria
Criteria
- 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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland | United States | 20892 |
Sponsors and Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
Investigators
- Principal Investigator: Joel Moss, M.D., National Heart, Lung, and Blood Institute (NHLBI)
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
- Finck-Barbançon V, Goranson J, Zhu L, Sawa T, Wiener-Kronish JP, Fleiszig SM, Wu C, Mende-Mueller L, Frank DW. ExoU expression by Pseudomonas aeruginosa correlates with acute cytotoxicity and epithelial injury. Mol Microbiol. 1997 Aug;25(3):547-57.
- Frank DW. The exoenzyme S regulon of Pseudomonas aeruginosa. Mol Microbiol. 1997 Nov;26(4):621-9. Review.
- Fu H, Coburn J, Collier RJ. The eukaryotic host factor that activates exoenzyme S of Pseudomonas aeruginosa is a member of the 14-3-3 protein family. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2320-4.
- 980062
- 98-H-0062