Pseudomonas aeruginosa persists as a major cause of life-threatening infections for individuals with the following conditions: cystic fibrosis, burns, wounds, cancer (leukemias), those receiving immunosuppressive therapy, diabetics, as well as intravenous drug users. The pili of this bacterium are protein filaments that extend from the ends of the cell. These structures serve as adhesion factors, and so are important virulence factors. Work from my laboratory has shown that the pill of P. aeruginosa 1244 are glycosylated with the O-antigen repeating unit of this organism. This trisaccharide moiety originates in the lipopolysaccharide O-antigen biosynthetic pathway. The long-term objectives of this project are to determine the role of pilus glycosylation in P. aeruginosa pathogenesis and to ascertain the importance of the glycan in pilus vaccine design. The work described in this proposal aims to determine the glycan and the pilin substrates in the P. aeruginosa 1244 pilin glycosylation reaction. In addition, the subcellular location of PilO, the enzyme that catalyzes pilin glycosylation in P. aeruginosa will be established. The membrane topology of this enzyme will also be determined. Finally, the subcellular location of the P. aeruginosa 1244 pilin glycosylation reaction established. ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI054929-05
Application #
7190560
Study Section
Special Emphasis Panel (ZRG1-BM-1 (02))
Program Officer
Taylor, Christopher E,
Project Start
2003-03-01
Project End
2009-02-28
Budget Start
2007-03-01
Budget End
2009-02-28
Support Year
5
Fiscal Year
2007
Total Cost
$145,757
Indirect Cost
Name
Duquesne University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
004501193
City
Pittsburgh
State
PA
Country
United States
Zip Code
15282
Allison, Tara M; Conrad, Sean; Castric, Peter (2015) The group I pilin glycan affects type IVa pilus hydrophobicity and twitching motility in Pseudomonas aeruginosa 1244. Microbiology 161:1780-9
Qutyan, Mohammed; Henkel, Matthew; Horzempa, Joseph et al. (2010) Glycosylation of pilin and nonpilin protein constructs by Pseudomonas aeruginosa 1244. J Bacteriol 192:5972-81
Horzempa, Joseph; Held, Thomas K; Cross, Alan S et al. (2008) Immunization with a Pseudomonas aeruginosa 1244 pilin provides O-antigen-specific protection. Clin Vaccine Immunol 15:590-7
Qutyan, Mohammed; Paliotti, Michael; Castric, Peter (2007) PilO of Pseudomonas aeruginosa 1244: subcellular location and domain assignment. Mol Microbiol 66:1444-58
Horzempa, Joseph; Comer, Jason E; Davis, Sheila A et al. (2006) Glycosylation substrate specificity of Pseudomonas aeruginosa 1244 pilin. J Biol Chem 281:1128-36