Abstract

The production of a mucoid capsular material, alginate, by P. aeruginosa is important for persistence of the pathogen in patients with cystic fibrosis. In previous work, Dr. Schiller demonstrated that alginate producing strains of P. aeruginosa also express alginate lyase, an enzyme that depolymerizes the mucopolysaccharides. Alginate lyase cleaves the 1-4 glycosidic linkage of L-guluronic-D-mannuronic polymers. The gene for alginate lyase (algL) was cloned and sequenced and mapped within an operon that contains the biosynthetic genes for alginate synthesis. algL is co-ordinately regulated with the alginate biosynthetic genes, indicating that this protein may serve a role in alginate synthesis or transport. The goals of this proposal are to define the role of algL and an upstream gene termed algX, in alginate synthesis, secretion, or chemical structure; to biochemically purify and characterize the activity of AlgL; to perform a structure/function analysis of AlgL; and to determine if AlgL is associated with other proteins. The long term objectives are to understand the mechanism of alginate synthesis and to contribute additional information regarding the activities of AlgL. This information may be useful in the rational design of enzyme inhibitors or the use of alginate lyase in the disruption of capsular material surrounding and protecting P. aeruginosa microcolonies from host immune responses and antibiotic treatment.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI036325-05
Application #
2886932
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Program Officer
Taylor, Christopher E
Project Start
1995-09-30
Project End
2000-08-31
Budget Start
1999-09-01
Budget End
2000-08-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost

  Institution

Name
University of California Riverside
Department
Type
Schools of Medicine
DUNS #
City
Riverside
State
CA
Country
United States
Zip Code
92521