""""""""Competence"""""""" refers to the ability of a bacterium to take up environmental DNA. Competence regulation in Bacillus subtilis involves a complex signal transduction network that governs the expression of a large regulon. This regulation is embedded in an even more extensive signal transduction network that governs several additional forms of post-exponential, global gene expression, e.g. sporulation and biofilm formation. Remarkably, competence, sporulation and biofilm formation are expressed bimodally and it is proposed to explore the regulatory mechanisms that govern bimodal gene expression, as well as to discover new examples of this type of expression. Additionally, the logic of the competence network and its relevant molecular interactions will be investigated using genetic, biochemical, microscopic and genomic approaches. In particular, the molecular interactions of the adaptor protein MecA will be studied as well as the modes of action of ComK as a novel transcription factor. The proposed work will also explore regulation on the cellular level, namely the mechanisms responsible for the dynamic localization of DNA uptake proteins to the cell poles. In this renewal application there is a new emphasis on generalizing and/or extending some of the concepts that have emerged from previous studies, particularly involving bimodal gene expression, MecA as a stochastic buffer and the cell biology of competence.

Public Health Relevance

Bacteria exchange genes and in this way can acquire antibiotic resistance and other new capabilities that increase virulence. The direct uptake of environmental DNA (transformation) is an important mechanism of such gene exchange in nature. The proposed work will explore the regulation of the genes that enable the uptake of DNA.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057720-43
Application #
8433391
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Maas, Stefan
Project Start
1977-06-01
Project End
2013-06-30
Budget Start
2013-03-01
Budget End
2013-06-30
Support Year
43
Fiscal Year
2013
Total Cost
$226,104
Indirect Cost
$81,167
Name
University of Medicine & Dentistry of NJ
Department
Public Health & Prev Medicine
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
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:
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
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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