Sophisticated strategies have emerged to regulate the critical vegetative / parasitic transition in all pathogens, and in many cases, this regulation is provided by two-component regulatory systems. The VirA/VirG system of the plant pathogen Agrobacterium tumefaciens is the model of a critical integrator of several different external signal inputs necessary for the commitment to pathogenesis. it is the only system for which the input signal is known and a model for signal perception exists. Moreover, the genetic and molecular tools to manipulate the genome are in place, allowing the factors that control vir gene expression to be easily and safely controlled in the pathogenetic organism itself. To seize this opportunity, we propose an experimental plan that allows us to test a molecular model for signal perception, integration, and transmission in pathogenetic signaling. The approach utilizes a wide range of chemical, physical, and genetic methods that exploit the resources available in different laboratories at two distinct institutions. The results of these studies will place us in the position to determine how signal input is recognized, integrated, and transduced in two-component response regulators. In addition, this specific signaling system regulates the only know natural vector for inter-Kingdom gene transfer and understanding this mechanism has already and will continue to widened the range of its use in biotechnology.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
2R01GM047369-09
Application #
6418688
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Program Officer
Jones, Warren
Project Start
1992-04-01
Project End
2005-12-31
Budget Start
2002-01-01
Budget End
2002-12-31
Support Year
9
Fiscal Year
2002
Total Cost
$447,488
Indirect Cost
Name
Emory University
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
042250712
City
Atlanta
State
GA
Country
United States
Zip Code
30322
Nair, Gauri R; Lai, Xiaoqin; Wise, Arlene A et al. (2011) The integrity of the periplasmic domain of the VirA sensor kinase is critical for optimal coordination of the virulence signal response in Agrobacterium tumefaciens. J Bacteriol 193:1436-48
Wise, Arlene A; Fang, Fang; Lin, Yi-Han et al. (2010) The receiver domain of hybrid histidine kinase VirA: an enhancing factor for vir gene expression in Agrobacterium tumefaciens. J Bacteriol 192:1534-42
He, Fanglian; Nair, Gauri R; Soto, Cinque S et al. (2009) Molecular basis of ChvE function in sugar binding, sugar utilization, and virulence in Agrobacterium tumefaciens. J Bacteriol 191:5802-13
Gao, Rong; Lynn, David G (2007) Integration of rotation and piston motions in coiled-coil signal transduction. J Bacteriol 189:6048-56
Yuan, Ze-Chun; Edlind, Merritt P; Liu, Pu et al. (2007) The plant signal salicylic acid shuts down expression of the vir regulon and activates quormone-quenching genes in Agrobacterium. Proc Natl Acad Sci U S A 104:11790-5
Maresh, Justin; Zhang, Jin; Tzeng, Yih-Ling et al. (2007) Rational design of inhibitors of VirA-VirG two-component signal transduction. Bioorg Med Chem Lett 17:3281-6
Wise, Arlene A; Liu, Zhenying; Binns, Andrew N (2006) Three methods for the introduction of foreign DNA into Agrobacterium. Methods Mol Biol 343:43-53
Maresh, Justin; Zhang, Jin; Lynn, David G (2006) The innate immunity of maize and the dynamic chemical strategies regulating two-component signal transduction in Agrobacterium tumefaciens. ACS Chem Biol 1:165-75
Wise, Arlene A; Liu, Zhenying; Binns, Andrew N (2006) Nucleic acid extraction from Agrobacterium strains. Methods Mol Biol 343:67-76
Wise, Arlene A; Liu, Zhenying; Binns, Andrew N (2006) Culture and maintenance of Agrobacterium strains. Methods Mol Biol 343:3-13

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