Abstract

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.

  Funding Agency

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

  Institution

Name
University of Rochester
Department
Microbiology/Immun/Virology
Type
Schools of Dentistry
DUNS #
208469486
City
Rochester
State
NY
Country
United States
Zip Code
14627

  Publications

Lamb, Janet R; Patel, Hetal; Montminy, Timothy et al. (2003) Functional domains of the RhlR transcriptional regulator of Pseudomonas aeruginosa. J Bacteriol 185:7129-39
Smith, Roger S; Harris, Sarah G; Phipps, Richard et al. (2002) The Pseudomonas aeruginosa quorum-sensing molecule N-(3-oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo. J Bacteriol 184:1132-9
Smith, Roger S; Kelly, Rodney; Iglewski, Barbara H et al. (2002) The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation. J Immunol 169:2636-42
De Kievit, T R; Gillis, R; Marx, S et al. (2001) Quorum-sensing genes in Pseudomonas aeruginosa biofilms: their role and expression patterns. Appl Environ Microbiol 67:1865-73
De Kievit, T R; Parkins, M D; Gillis, R J et al. (2001) Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 45:1761-70
McKnight, S L; Iglewski, B H; Pesci, E C (2000) The Pseudomonas quinolone signal regulates rhl quorum sensing in Pseudomonas aeruginosa. J Bacteriol 182:2702-8
Hassett, D J; Ma, J F; Elkins, J G et al. (1999) Quorum sensing in Pseudomonas aeruginosa controls expression of catalase and superoxide dismutase genes and mediates biofilm susceptibility to hydrogen peroxide. Mol Microbiol 34:1082-93
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

Showing the most recent 10 out of 24 publications