Pseudomonas aeruginosa is an important cause of
disease in immunocompromised persons, as well as persons with burns or
cystic fibrosis. Virulence of P. aeruginosa is multifactorial
and involves both cell associated structures such as pili and secreted
products such as exotoxin A and proteases. The molecular mechanisms by
which these products are regulated are poorly understood.
Our work has shown that expression of three of the four known P.
aeruginosa protease genes (lasA, lasB and aprA) encoding the
extracellular proteases, LasA, elastase and alkaline protease, are
positively regulated, in trans, by the lasR protein. LasR is
homologous to the well characterized luxR protein. Recently, we have
also cloned and sequenced the lasI gene, adjacent to lasR, and found
its protein to be homologous to Luxl. The existence of lasR and lasI
provides P. aeruginosa a system by which it can communicate to
other (P. aeruginosa) cells, to begin to express proteases
which, in turn, leads to host tissue damage and bacterial
dissemination. This is a novel concept in bacterial pathogenesis.
Ongoing studies are aimed at understanding the regulation of lasR and
lasI, and relating their expression to the expression of other P.
aeruginosa genes, including the protease gene. Additional studies
are examining the structure and function of the LasR protein and the cis-acting
sequences from the lasB, lasA and aprA genes which are influenced by
LasR and LasI. These experiments should provide insight into how
virulence is regulated in P. aeruginosa.
Functional Genomics: Cutting-edge technologies such
as gene expression analysis are being used to unravel the biology of
Pseudomonas aeruginosa's adaptation to the CF lung and how the cells
within the lung respond to this bacterium.
Biographical Information
Dr. Iglewski, Ph.D., is a 2001 recipient of the Susan B. Anthony
Lifetime Achievement Award. Dr. Iglewski graduated from Allegheny
College in 1960 with a B.S. in biology and went on to complete her
Ph.D. in microbiology at Pennsylvania State University. After several
years spent researching and teaching at the University of Colorado, the
Public Health Research Institute of New York City, and at the Oregon
Health Services University, she came to the University of Rochester
School of Medicine and Dentistry as professor and chair of the
Department of Microbiology and Immunology in 1986. Dr. Iglewski was the
first woman to chair a department at the Medical School.
Supplemental Data for Recent Publications
Supplemental data for:
Microarray Analysis of Pseudomonas aeruginosa Quorum-Sensing Regulons:
Effects of Growth Phase and Environment. V.E. Wagner, D. Bushnell, L.
Passador, A.I. Brooks, and B.H. Iglewski. J Bacteriol. 185:2080-2095,
2003.
Supplemental data for:
Effect of Anaerobiosis and Nitrate on Gene Expression of Pseudomonas
aeruginosa. M. J. Filiatrault, V.E. Wagner, D. Bushnell, C.G. Haidaris,
B. H. Iglewski, and L. Passador. 2005. Infection and Immunity.73(6):
XXX-XXX
Recent Publications
Filiatrault, M.J., V.E.Wagner, D. Bushnell, C.G.Haidaris, B.H. Iglewski and L. Passador Effect of Anaerobiosis and Nitrate on Gene Expression in Pseudomonas aeruginosa. Infect. Immun. 73, June 2005 ( in press).
Imamura Y, Higashiyama Y, Tomono K, Izumikawa K, Yanagihara K, Ohno H, Miyazaki Y, Hirakata Y, Mizuta Y, Kadota J, Iglewski BH, Kohno S. Azithromycin Exhibits Bactericidal Effects on Pseudomonas aeruginosa through Interaction with the Outer Membrane.
Antimicrob Agents Chemother. 2005 Apr;49(4):1377-80.
Gillis RJ, Iglewski BH. Azithromycin retards Pseudomonas aeruginosa biofilm formation.
J Clin Microbiol. 2004 Dec;42(12):5842-5.
Wagner VE, Gillis RJ, Iglewski BH. Transcriptome analysis of quorum-sensing regulation and virulence factor expression in Pseudomonas aeruginosa.Vaccine. 2004 Dec 6;22 Suppl 1:S15-20.
Lamb JR, Patel H, Montminy T, Wagner VE, Iglewski BH. Functional domains of the RhlR transcriptional regulator of Pseudomonas aeruginosa.
J Bacteriol. 2003 Dec;185(24):7129-39.
Pseudomonas aeruginosa quorum sensing as a potential antimicrobial target.
J Clin Invest. 2003 Nov;112(10):1460-5.
Wagner VE, Bushnell D, Passador L, Brooks AI, Iglewski BH. Microarray analysis of Pseudomonas aeruginosa quorum-sensing regulons: effects of growth phase and environment.
J Bacteriol. 2003 Apr;185(7):2080-95
Smith RS, Iglewski BH. P. aeruginosa quorum-sensing systems and virulence.
Curr Opin Microbiol. 2003 Feb;6(1):56-60. Review.
Yoon SS, Hennigan RF, Hilliard GM, Ochsner UA, Parvatiyar K, Kamani MC, Allen HL, DeKievit TR, Gardner PR, Schwab U, Rowe JJ, Iglewski BH, McDermott TR, Mason RP, Wozniak DJ, Hancock RE, Parsek MR, Noah TL, Boucher RC, Hassett DJ. Pseudomonas aeruginosa anaerobic respiration in biofilms: relationships to cystic fibrosis pathogenesis.
Dev Cell. 2002 Oct;3(4):593-603.
Smith RS, Kelly R, Iglewski BH, Phipps RP. The Pseudomonas autoinducer N-(3-oxododecanoyl) homoserine lactone induces cyclooxygenase-2 and prostaglandin E2 production in human lung fibroblasts: implications for inflammation.
J Immunol. 2002 Sep 1;169(5):2636-42.
de Kievit TR, Kakai Y, Register JK, Pesci EC, Iglewski BH. Role of the Pseudomonas aeruginosa las and rhl quorum-sensing systems in rhlI regulation.
FEMS Microbiol Lett. 2002 Jun 18;212(1):101-6.
Smith RS, Harris SG, Phipps R, Iglewski B. The Pseudomonas aeruginosa quorum-sensing molecule N-(3- oxododecanoyl)homoserine lactone contributes to virulence and induces inflammation in vivo.
J Bacteriol. 2002 Feb;184(4):1132-9.
Smith RS, Fedyk ER, Springer TA, Mukaida N, Iglewski BH, Phipps RP. IL-8 production in human lung fibroblasts and epithelial cells activated by the Pseudomonas autoinducer N-3-oxododecanoyl homoserine lactone is transcriptionally regulated by NF-kappa B and activator protein-2.
J Immunol. 2001 Jul 1;167(1):366-74.
De Kievit TR, Parkins MD, Gillis RJ, Srikumar R, Ceri H, Poole K, Iglewski BH, Storey DG. Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms.
Antimicrob Agents Chemother. 2001 Jun;45(6):1761-70.
PubMed Publication List
Links
|
