"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 #
5R01GM057720-42
Application #
8241131
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Maas, Stefan
Project Start
1977-06-01
Project End
2014-02-28
Budget Start
2012-03-01
Budget End
2013-02-28
Support Year
42
Fiscal Year
2012
Total Cost
$615,470
Indirect Cost
$220,938
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
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; Desai, Yaanik; Raj, Arjun et al. (2012) Spo0A~P imposes a temporal gate for the bimodal expression of competence in Bacillus subtilis. PLoS Genet 8:e1002586
Mirouze, Nicolas; Prepiak, Peter; Dubnau, David (2011) Fluctuations in spo0A transcription control rare developmental transitions in Bacillus subtilis. PLoS Genet 7:e1002048
Dubnau, D (2011) Winner takes all in a race for cell fate. Mol Syst Biol 7:558
Briley Jr, Kenneth; Prepiak, Peter; Dias, Miguel J et al. (2011) Maf acts downstream of ComGA to arrest cell division in competent cells of B. subtilis. Mol Microbiol 81:23-39
Prepiak, Peter; Defrancesco, Melissa; Spadavecchia, Sophia et al. (2011) MecA dampens transitions to spore, biofilm exopolysaccharide and competence expression by two different mechanisms. Mol Microbiol 80:1014-30
Mirouze, Nicolas; Parashar, Vijay; Baker, Melinda D et al. (2011) An atypical Phr peptide regulates the developmental switch protein RapH. J Bacteriol 193:6197-206
Parashar, Vijay; Mirouze, Nicolas; Dubnau, David A et al. (2011) Structural basis of response regulator dephosphorylation by Rap phosphatases. PLoS Biol 9:e1000589
Burton, Briana; Dubnau, David (2010) Membrane-associated DNA transport machines. Cold Spring Harb Perspect Biol 2:a000406
Dubnau, David (2010) Swim or chill: lifestyles of a bacillus. Genes Dev 24:735-7

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