Genetic competence is defined as a state in which bacterial cells are able to bind and internalize high molecular weight DMA,which may then be established as an independent replicon or recombine with a resident DMA molecule. Competence in Bacillus subtilis is one of several post-exponentially expressed systems, the most extensively studied of which is sporulation. The present study is directed towards unraveling the complex regulatory network that determines the onset of competence expression in response to environmental signals. This network is known to rely on quorum sensing, transmembrane signaling, phosphorylation events involving two-component regulators, protein-protein and protein-DNA interactions, transcriptional and posttranscriptional regulation as well as the action of CIpC, a AAA+ protein. We will investigate the interaction of ComP with the quorum-sensing ComX pheromones. We will study the interactions of MecA; CIpC and ComS which regulate the stability of the competence-specific transcription factor ComK. We will investigate the interactions of the five proteins known to bind at the comK promoter. We will study the factors responsible for the bistable expression of competence, the competence-specific growth arrest and the regulation of competence protein localization and delocalization in the cell. Quorum sensing and the CIpC heat shock protein regulate pathogenesis in a number of bacterial pathogens. Understanding the biology of the proteins involved may help to clarify the virulence mechanisms involved.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057720-38
Application #
7329151
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Anderson, James J
Project Start
1977-06-01
Project End
2009-11-30
Budget Start
2007-12-01
Budget End
2008-11-30
Support Year
38
Fiscal Year
2008
Total Cost
$544,771
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
623946217
City
Newark
State
NJ
Country
United States
Zip Code
07107
Tanner, Andrew W; Carabetta, Valerie J; Dubnau, David (2018) ClpC and MecA, components of a proteolytic machine, prevent Spo0A-P-dependent transcription without degradation. Mol Microbiol 108:178-186
Diethmaier, Christine; Chawla, Ravi; Canzoneri, Alexandra et al. (2017) Viscous drag on the flagellum activates Bacillus subtilis entry into the K-state. Mol Microbiol 106:367-380
Carabetta, Valerie J; Cristea, Ileana M (2017) Regulation, Function, and Detection of Protein Acetylation in Bacteria. J Bacteriol 199:
Tanner, Andrew W; Carabetta, Valerie J; Martinie, Ryan J et al. (2017) The RicAFT (YmcA-YlbF-YaaT) complex carries two [4Fe-4S]2+ clusters and may respond to redox changes. Mol Microbiol 104:837-850
Dubnau, Eugenie J; Carabetta, Valerie J; Tanner, Andrew W et al. (2016) A protein complex supports the production of Spo0A-P and plays additional roles for biofilms and the K-state in Bacillus subtilis. Mol Microbiol 101:606-24
Miras, Mathieu; Dubnau, David (2016) A DegU-P and DegQ-Dependent Regulatory Pathway for the K-state in Bacillus subtilis. Front Microbiol 7:1868
Carabetta, Valerie J; Greco, Todd M; Tanner, Andrew W et al. (2016) Temporal Regulation of the Bacillus subtilis Acetylome and Evidence for a Role of MreB Acetylation in Cell Wall Growth. mSystems 1:
Hahn, Jeanette; Tanner, Andrew W; Carabetta, Valerie J et al. (2015) ComGA-RelA interaction and persistence in the Bacillus subtilis?K-state. Mol Microbiol 97:454-71
Carabetta, Valerie J; Tanner, Andrew W; Greco, Todd M et al. (2013) A complex of YlbF, YmcA and YaaT regulates sporulation, competence and biofilm formation by accelerating the phosphorylation of Spo0A. Mol Microbiol 88:283-300
Mirouze, Nicolas; Dubnau, David (2013) Chance and Necessity in Bacillus subtilis Development. Microbiol Spectr 1:

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