The vast majority of all known two-component systems regulate gone expression in response to environmental stimuli with one notable exception being the chemotaxis system that regulates motility. Analysis of the Che3 chemosensory system in Myxococcus xanthus led to the surprising discovery, however, that this chemotaxis-like signal transduction system affects developmentally regulated gone expression without affecting motility or chemotaxis. Although the Che3 system comprises homologs to CheA, CheB, CheR, CheW, and two chemoreceptors (MCPs), the output of the system is unusual with respect to the prototype found in E. coli for the control of motility. The output of the Che3 system is not mediated by CheY but feeds through CrdA, a homolog of the NtrC family of sigma54-dependent transcriptional activators and thereby affects gene expression. Knowledge of the M. xanthus Che3 system will have important implications for our understanding of the broader fields of two-component signal transduction ranging from the control of prokaryotic development to biofilm formation and antibiotic resistance. The overall goal of this project is to fully characterize the signaling pathway comprising the M. xanthus Che3 system. To understand the mechanism of chemosensory regulation of gene expression and its role in development of M. xanthus, four specific aims are proposed: 1) characterize the phosphorelay component of the signaling pathway, 2) characterize the receptor signaling complex, 3) analyze the role of methylation-dependent adaptation, and 4) identify the output controlled by the Che3 system.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Research Project (R01)
Project #
5R01AI059682-02
Application #
6985399
Study Section
Microbial Physiology and Genetics Subcommittee 2 (MBC)
Program Officer
Korpela, Jukka K
Project Start
2004-12-01
Project End
2009-11-30
Budget Start
2005-12-01
Budget End
2006-11-30
Support Year
2
Fiscal Year
2006
Total Cost
$286,893
Indirect Cost
Name
Georgia Institute of Technology
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
097394084
City
Atlanta
State
GA
Country
United States
Zip Code
30332
Willett, Jonathan W; Kirby, John R (2012) Genetic and biochemical dissection of a HisKA domain identifies residues required exclusively for kinase and phosphatase activities. PLoS Genet 8:e1003084
Willett, Jonathan W; Kirby, John R (2011) CrdS and CrdA comprise a two-component system that is cooperatively regulated by the Che3 chemosensory system in Myxococcus xanthus. MBio 2:
Scharf, Birgit E; Aldridge, Phillip D; Kirby, John R et al. (2009) Upward mobility and alternative lifestyles: a report from the 10th biennial meeting on Bacterial Locomotion and Signal Transduction. Mol Microbiol 73:5-19
Berleman, James E; Kirby, John R (2009) Deciphering the hunting strategy of a bacterial wolfpack. FEMS Microbiol Rev 33:942-57
Kirby, John R (2009) Chemotaxis-like regulatory systems: unique roles in diverse bacteria. Annu Rev Microbiol 63:45-59
Mignot, Tam; Kirby, John R (2008) Genetic circuitry controlling motility behaviors of Myxococcus xanthus. Bioessays 30:733-43
Berleman, James E; Scott, Jodie; Chumley, Tatiana et al. (2008) Predataxis behavior in Myxococcus xanthus. Proc Natl Acad Sci U S A 105:17127-32
Zusman, David R; Scott, Ansley E; Yang, Zhaomin et al. (2007) Chemosensory pathways, motility and development in Myxococcus xanthus. Nat Rev Microbiol 5:862-72
Berleman, James E; Kirby, John R (2007) multicellular development in Myxococcus xanthus is stimulated by predator-prey interactions. J Bacteriol 189:5675-82
Berleman, James E; Chumley, Tatiana; Cheung, Patricia et al. (2006) Rippling is a predatory behavior in Myxococcus xanthus. J Bacteriol 188:5888-95

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