The long term goal of this research is to determine the role of autoinduction or quorum sensing in the pathogenesis of P. aeruginosa. Previous studies have shown that LasR (regulatory protein) interacts with an autoinducer, PAI, to activate transcription of virulence genes (lasB, lasA, aprA, and toxA) related to tissue destruction and possibly dissemination. By studying the regulatory pathway leading to production of these virulence factors an additional autoinducer molecule was discovered, purified, and characterized which is termed factor 2. This proposal will focus on a structure-function analysis of the autoinducers, their targets, and the role that these molecules serve in transcriptional activation of various genes involved in protease production. The results will further our understanding of the regulation of virulence in P. aeruginosa and provide new insights into quorum sensing systems.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI033713-05
Application #
2003911
Study Section
Special Emphasis Panel (ZRG5-BM-2 (04))
Project Start
1993-01-01
Project End
2000-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627
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Pesci, E C; Milbank, J B; Pearson, J P et al. (1999) Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 96:11229-34
Glessner, A; Smith, R S; Iglewski, B H et al. (1999) Roles of Pseudomonas aeruginosa las and rhl quorum-sensing systems in control of twitching motility. J Bacteriol 181:1623-9
Kline, T; Bowman, J; Iglewski, B H et al. (1999) Novel synthetic analogs of the Pseudomonas autoinducer. Bioorg Med Chem Lett 9:3447-52

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