Role of Toxins in Lung Infections Caused by Pseudomonas Aeruginosa

Role of Exotoxins in the Pathogenesis of Pseudomonas Aeruginosa

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....

Study Overview

• Status: Completed
• Conditions: Cystic Fibrosis; Pseudomonas Infection

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 Type: Observational
• Enrollment (Actual): 134

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 9 years to 99 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

patients with cystic fibrosis being treated with antibiotics, patients with cystic fibrosis who have not undergone antibiotic therapy, and control patients.@@@@@@

Description

• 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
1; Healthy Volunteers
2; Cystic Fibrosis subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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

Collaborators and Investigators

• Sponsor: National Heart, Lung, and Blood Institute (NHLBI)

Publications and helpful links

General Publications

• Finck-Barbancon 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. doi: 10.1046/j.1365-2958.1997.4891851.x.
• 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. doi: 10.1073/pnas.90.6.2320.
• Frank DW. The exoenzyme S regulon of Pseudomonas aeruginosa. Mol Microbiol. 1997 Nov;26(4):621-9. doi: 10.1046/j.1365-2958.1997.6251991.x.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): March 17, 1998
• Primary Completion (Actual): September 7, 2006
• Study Completion (Actual): December 28, 2018

Study Registration Dates

• First Submitted: November 27, 2001
• First Submitted That Met QC Criteria: November 27, 2001
• First Posted (Estimate): November 28, 2001

Study Record Updates

• Last Update Posted (Actual): June 6, 2022
• Last Update Submitted That Met QC Criteria: June 3, 2022
• Last Verified: June 1, 2022

More Information

Terms related to this study

• Keywords: Natural History; Cystic Fibrosis; Cytotoxin; Lung Injury; Effector Proteins; Genetic Screen
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Infant, Newborn, Diseases; Genetic Diseases, Inborn; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pancreatic Diseases; Fibrosis; Infections; Cystic Fibrosis; Pseudomonas Infections
• Other Study ID Numbers: 980062; 98-H-0062