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.
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.
|Hughes, Anna C; Subramanian, Sundharraman; Dann 3rd, Charles E et al. (2018) The C-Terminal Region of Bacillus subtilis SwrA Is Required for Activity and Adaptor-Dependent LonA Proteolysis. J Bacteriol 200:|
|Burrage, Andrew M; Vanderpool, Eric; Kearns, Daniel B (2018) The assembly order of flagellar rod subunits in Bacillus subtilis. J Bacteriol :|
|Hall, Ashley N; Subramanian, Sundharraman; Oshiro, Reid T et al. (2018) SwrD (YlzI) Promotes Swarming in Bacillus subtilis by Increasing Power to Flagellar Motors. J Bacteriol 200:|
|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|
|Li, Ye; Zhai, He; Sanchez, Sandra et al. (2017) Noncontact Cohesive Swimming of Bacteria in Two-Dimensional Liquid Films. Phys Rev Lett 119:018101|
|Ilkanaiv, Bella; Kearns, Daniel B; Ariel, Gil et al. (2017) Effect of Cell Aspect Ratio on Swarming Bacteria. Phys Rev Lett 118:158002|
|Berger, Angela K; Yi, Hong; Kearns, Daniel B et al. (2017) Bacteria and bacterial envelope components enhance mammalian reovirus thermostability. PLoS Pathog 13:e1006768|
|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|
|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|
Showing the most recent 10 out of 45 publications