An important feature of Pseudomonas aeruginosa pathogenesis is the ability to form surface- associated communities called biofilms. Several types of P. aeruginosa infections are characterized by biofilm formation, including the colonization of indwelling medical devices and the chronic infections present in the airways of people suffering from cystic fibrosis (CF). Biofilm bacteria produce one or more extracellular polymeric substances (EPS) that act as a scaffold, holding biofilm cells together and to a surface. For some time, alginate has been considered the major polysaccharide of the P. aeruginosa EPS biofilm matrix. Recently, our studies indicate that alginate is not a significant component of the EPS matrix of nonmucoid strains, which are responsible for most opportunistic biofilm infections and are also the first to colonize CF patients. Instead, there appear to be other EPS components that mediate biofilm formation. Our lab and others discovered that P. aeruginosa has the capacity to encode two alternative polysaccharides, designated Psl and Pel, which play critical roles in cell surface interactions and biofilm formation. The focus of this proposal is the Pel gene cluster. Our overall objective is to determine the role of Pel in biofilm development, structure, resistance to antimicrobial agents, and pathogenesis. A further understanding of this critical biofilm component will lead to strategies aimed at inhibiting biofilm formation, a key aspect of P. aeruginosa pathogenesis. Despite significant advancements in our knowledge of P. aeruginosa biofilm development, there remain gaps in our understanding of the biofilm matrix composition, as well as the genes responsible for producing this matrix. We have discovered a novel EPS locus that is essential for formation of P. aeruginosa biofilms. Since the matrix provides a critical protective role as well as a scaffold for the developing biofilm, agents aimed at disrupting the matrix would have therapeutic value. A thorough analysis of Pel may lead to the development of such agents and improve the quality of life for C patients as well as individuals with other P. aeruginosa infections that involve biofilms.

Public Health Relevance

is proposal is focused on examining the role of the important biofilm exopolysaccharide Pel in Pseudomonas aeruginosa biofilm formation and pathogenesis. The role of Pel in polysaccharide production, biofilm formation and pathogenesis will be explored.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI077628-04
Application #
8300158
Study Section
Bacterial Pathogenesis Study Section (BACP)
Program Officer
Taylor, Christopher E,
Project Start
2009-07-17
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2014-06-30
Support Year
4
Fiscal Year
2012
Total Cost
$493,942
Indirect Cost
$174,396
Name
University of Washington
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195
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Parsek, Matthew R (2016) Controlling the Connections of Cells to the Biofilm Matrix. J Bacteriol 198:12-4
Tseng, Boo Shan; Majerczyk, Charlotte D; Passos da Silva, Daniel et al. (2016) Quorum Sensing Influences Burkholderia thailandensis Biofilm Development and Matrix Production. J Bacteriol 198:2643-50
Jennings, Laura K; Storek, Kelly M; Ledvina, Hannah E et al. (2015) Pel is a cationic exopolysaccharide that cross-links extracellular DNA in the Pseudomonas aeruginosa biofilm matrix. Proc Natl Acad Sci U S A 112:11353-8
Hmelo, Laura R; Borlee, Bradley R; Almblad, Henrik et al. (2015) Precision-engineering the Pseudomonas aeruginosa genome with two-step allelic exchange. Nat Protoc 10:1820-41
Park, Jin Hwan; Jo, Youmi; Jang, Song Yee et al. (2015) The cabABC Operon Essential for Biofilm and Rugose Colony Development in Vibrio vulnificus. PLoS Pathog 11:e1005192
Almblad, Henrik; Harrison, Joe J; Rybtke, Morten et al. (2015) The Cyclic AMP-Vfr Signaling Pathway in Pseudomonas aeruginosa Is Inhibited by Cyclic Di-GMP. J Bacteriol 197:2190-200
Cohen, Dorit; Mechold, Undine; Nevenzal, Hadas et al. (2015) Oligoribonuclease is a central feature of cyclic diguanylate signaling in Pseudomonas aeruginosa. Proc Natl Acad Sci U S A 112:11359-64
Colvin, Kelly M; Alnabelseya, Noor; Baker, Perrin et al. (2013) PelA deacetylase activity is required for Pel polysaccharide synthesis in Pseudomonas aeruginosa. J Bacteriol 195:2329-39
Zhao, Kun; Tseng, Boo Shan; Beckerman, Bernard et al. (2013) Psl trails guide exploration and microcolony formation in Pseudomonas aeruginosa biofilms. Nature 497:388-91

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