Bacterial populations, once thought to be uniform, are in fact heterogeneous mixtures of distinct cell types that become apparent when studied at the level of individual cells. Bistable (ON/OFF) gene expression epigenetically results in cell type differentiation and creates subpopulations predisposed to exploit/survive environmental change. Here we explore the unique features of the bistable expression of motility genes in Bacillus subtilis that generates mixed populations of single motile cells and non-motile chains through an epigenetic mechanism. We will measure the kinetics of switching between motility-ON and motility-OFF states and the inheritance of each state during growth. We will determine the mechanism by which the alternative sigma factor CD is controlled by both a gradual decline in transcript levels along a 27 kb operon, and regulation in response to flagellar assembly, to produce bistable gene expression. Finally, we will determine the mechanism by which a developmental regulator of unknown function, SwrA, biases the proportion of the population that is in an ON or OFF state. Motility and its control has been long-studied in Gram negative bacteria like E. coli and we intend to elevate the evolutionarily distant Gram positive B. subtilis to a premiere model system for the discovery of new paradigms of motility gene regulation. Bistability is an important new area of prokaryotic research that changes the way we think about bacterial populations. The information we gather will be directly relevant to bacterial development, antibiotic therapy, virulence gene expression, and bacterial pathogenesis.

Public Health Relevance

We will study flagellar-mediated motility in Bacillus subtilis and we will determine the kinetics, mechanism, and regulation of a bistable epigenetic switching controlling flagellin and autolysin expression.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
1R01GM093030-01
Application #
7861445
Study Section
Prokaryotic Cell and Molecular Biology Study Section (PCMB)
Program Officer
Anderson, James J
Project Start
2010-07-15
Project End
2015-06-30
Budget Start
2010-07-15
Budget End
2011-06-30
Support Year
1
Fiscal Year
2010
Total Cost
$286,080
Indirect Cost
Name
Indiana University Bloomington
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
006046700
City
Bloomington
State
IN
Country
United States
Zip Code
47401
Subramanian, Sundharraman; Gao, Xiaohui; Dann 3rd, Charles E et al. (2017) MotI (DgrA) acts as a molecular clutch on the flagellar stator protein MotA in Bacillus subtilis. Proc Natl Acad Sci U S A 114:13537-13542
Farley, Madeline M; Tu, Jiagang; Kearns, Daniel B et al. (2017) Ultrastructural analysis of bacteriophage ?29 during infection of Bacillus subtilis. J Struct Biol 197:163-171
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
Hummels, Katherine R; Witzky, Anne; Rajkovic, Andrei et al. (2017) Carbonyl reduction by YmfI in Bacillus subtilis prevents accumulation of an inhibitory EF-P modification state. Mol Microbiol 106:236-251
Ilkanaiv, Bella; Kearns, Daniel B; Ariel, Gil et al. (2017) Effect of Cell Aspect Ratio on Swarming Bacteria. Phys Rev Lett 118:158002
Wang, Fengbin; Burrage, Andrew M; Postel, Sandra et al. (2017) A structural model of flagellar filament switching across multiple bacterial species. Nat Commun 8:960
Nye, Taylor M; Schroeder, Jeremy W; Kearns, Daniel B et al. (2017) Complete Genome Sequence of Undomesticated Bacillus subtilis Strain NCIB 3610. Genome Announc 5:
Myagmarjav, B-E; Konkol, M A; Ramsey, J et al. (2016) ZpdN, a Plasmid-Encoded Sigma Factor Homolog, Induces pBS32-Dependent Cell Death in Bacillus subtilis. J Bacteriol 198:2975-2984
Liu, Bo; Kearns, Daniel B; Bechhofer, David H (2016) Expression of multiple Bacillus subtilis genes is controlled by decay of slrA mRNA from Rho-dependent 3' ends. Nucleic Acids Res 44:3364-72
Abbott, Zachary D; Flynn, Kaitlin J; Byrne, Brenda G et al. (2016) csrT Represents a New Class of csrA-Like Regulatory Genes Associated with Integrative Conjugative Elements of Legionella pneumophila. J Bacteriol 198:553-64

Showing the most recent 10 out of 40 publications