Abstract

Natural transformation in bacteria is an important mode of horizontal gene transfer. Generally, it contributes to bacterial evolution and specifically to the spread of antibiotic resistance and virulence genes. This proposal will use Bacillus subtilis as a model to address the fundamental, largely conserved mechanisms that enable the uptake of environmental DNA. It will address the binding of DNA to the surface of the cell, traversal through the cell wall and translocation of DNA across the cell membrane. This plan will provide broad insights into molecular details of transformation and will bring us closer to the long-term goal of understanding the mechanism of DNA uptake. It is proposed to investigate the energy sources for DNA uptake, the proteins involved, some of their structures and their interactions as components of a molecular machine.
These aims will be pursued using the tools of cell biology, genetics, biochemistry and structural biology.

Public Health Relevance

Natural transformation is an important mode of horizontal gene transfer in bacteria, contributing to the spread of antibiotic resistance and of virulence genes as well as to immune evasion. This proposal will elucidate molecular mechanisms that enable the uptake of environmental DNA.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM057720-50
Application #
9982368
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Xu, Jianhua
Project Start
1977-06-01
Project End
2023-06-30
Budget Start
2020-07-01
Budget End
2021-06-30
Support Year
50
Fiscal Year
2020
Total Cost
Indirect Cost

  Institution

Name
Rutgers University
Department
Public Health & Prev Medicine
Type
Schools of Medicine
DUNS #
078795851
City
Newark
State
NJ
Country
United States
Zip Code
07103

  Publications

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:

Showing the most recent 10 out of 49 publications