To characterize non-toxic, effective anti-biofilm agents that do not affect bacterial growth, a research program is proposed to investigate the ability of naturally-occurring marine furanones and other plant-derived compounds to inhibit the formation of E. coli biofilms. In addition, the genetic basis of biofilm formation will be investigated using temporal DNA microarray studies, knock-outs, and NMR structure determinations of the discovered biofilm regulatory proteins. This project will discover the genes required for E. coli biofilm formation by two complementary approaches using DNA microarrays: direct identification of biofilm genes and by inhibiting biofilms with plant compounds. In addition, this project will identify how the plant-derived biofilm inhibitors influence biofilms, and will discover other plant-derived compounds which inhibit biofilms. The biofilm genes that are found will be rich targets for other classes of compounds that may be used to prevent biofilms in industry and medicine. The specific objectives of this project are: 1. synthesize natural furanones from the red alga Delisea pulchra and evaluate these furanones and other plant-derived compounds for their ability to prevent biofilm formation using confocal microscopy and 96-well rapid assays 2. evaluate the impact of the plant-derived inhibitors on the gene expression of E. coli using DNA microarrays (identify which genes are affected while the inhibitor does not affect growth) 3. discover biofilm genes using DNA microarrays for E. coli (submerged biofilm) 4. discover cell-to-cell signaling genes using DNA microarrays by inhibiting communication with furanones 5. study the importance of the genes elucidated with the gene chips in terms of biofilm formation and architecture using knock-out mutants that are labeled with the green fluorescence protein and by tagging the promoters of biofilm regulatory proteins 6. determine the structure and thereby the function of the important biofilm regulatory proteins using NMR 7. deduce a model for bacterial biofilm formation based on the genetic information (which genes induced/repressed) and protein information discerned (via NMR)

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB003872-04
Application #
7248685
Study Section
Special Emphasis Panel (ZRG1-IDM-H (10))
Program Officer
Henderson, Lori
Project Start
2005-07-19
Project End
2009-04-30
Budget Start
2007-05-01
Budget End
2008-04-30
Support Year
4
Fiscal Year
2007
Total Cost
$294,105
Indirect Cost
Name
Texas Engineering Experiment Station
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
847205572
City
College Station
State
TX
Country
United States
Zip Code
77845
Wang, Xiaoxue; Kim, Younghoon; Hong, Seok Hoon et al. (2011) Antitoxin MqsA helps mediate the bacterial general stress response. Nat Chem Biol 7:359-66
Ma, Qun; Yang, Zhonghua; Pu, Mingming et al. (2011) Engineering a novel c-di-GMP-binding protein for biofilm dispersal. Environ Microbiol 13:631-42
Kim, Younghoon; Wang, Xiaoxue; Zhang, Xue-Song et al. (2010) Escherichia coli toxin/antitoxin pair MqsR/MqsA regulate toxin CspD. Environ Microbiol 12:1105-21
Ueda, Akihiro; Wood, Thomas K (2010) Tyrosine Phosphatase TpbA of Pseudomonas aeruginosa Controls Extracellular DNA via Cyclic Diguanylic Acid Concentrations. Environ Microbiol 2:449-55
Kim, Younghoon; Wood, Thomas K (2010) Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli. Biochem Biophys Res Commun 391:209-13
Hong, Seok Hoon; Wang, Xiaoxue; Wood, Thomas K (2010) Controlling biofilm formation, prophage excision and cell death by rewiring global regulator H-NS of Escherichia coli. Microb Biotechnol 3:344-56
Bansal, Tarun; Alaniz, Robert C; Wood, Thomas K et al. (2010) The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci U S A 107:228-33
Hong, Seok Hoon; Lee, Jintae; Wood, Thomas K (2010) Engineering global regulator Hha of Escherichia coli to control biofilm dispersal. Microb Biotechnol 3:717-28
Ueda, Akihiro; Attila, Can; Whiteley, Marvin et al. (2009) Uracil influences quorum sensing and biofilm formation in Pseudomonas aeruginosa and fluorouracil is an antagonist. Microb Biotechnol 2:62-74
Hegde, Manjunath; Wood, Thomas K; Jayaraman, Arul (2009) The neuroendocrine hormone norepinephrine increases Pseudomonas aeruginosa PA14 virulence through the las quorum-sensing pathway. Appl Microbiol Biotechnol 84:763-76

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