The cell envelope is an essential yet highly dynamic structure that protects the bacterial cell from its environment. Maintaining its integrity throughout the growth cycle - even in the face of antibiotic threat - is absolutely essential for survival. While significant progress has been made in recent years on understanding envelope homeostasis during balanced growth, little is known on the regulatory and physiological adjustments in stationary phase. The goal of the project is to study how bacteria maintain cell envelope homeostasis during the complex differentiation cascade of Bacillus subtilis during stationary phase. Within this differentiation process, a subpopulation of cells produces antimicrobial peptides (AMPs) that not only interfere with cell wall biosynthesis of competing species, but also target subpopulations of B. subtilis cells in a process termed cannibalism. Since many AMPs inhibit active cell wall biosynthesis, it seems likely that only a subpopulation of cells that are still vegetative in stationary phase is susceptible to AMP action. Moreover, we previously showed that in stationary phase B. subtilis induces parts of the cell envelope stress response (CESR) to defend against AMP attack, but it does so only in a small subpopulation of cells (Dominguez-Escobar et al., 2014). However, to date it is unknown how the heterogeneous stationary phase traits of AMP production, cell growth and the induction of the CESR are correlated at the single cell level and how this would result in a concerted survival strategy in stationary phase. To study these questions, we combine experimental approaches from molecular biology with mathematical modeling approaches from theoretical physics. Ultimately, we would like to unravel the physiological relevance of phenotypic heterogeneity in cell envelope homeostasis and Lia-mediated CESR for stationary phase survival.
References:
- List of publications (T. Mascher)
- List of publications (G. Fritz)
Contact details:
Prof. Dr. Thorsten Mascher
Technische Universität (TU) Dresden
Institut für Mikrobiologie
Lehrstuhl für Allgemeine Mikrobiologie
Zellescher Weg 20b
01217 Dresden
Tel.: +49-(0)351 / 463-40420
Fax.: +49-(0)351 / 463-37715
thorsten.mascher(at)tu-dresden.de
Homepage Link
Dr. Georg Fritz
LOEWE-Zentrum für Synthetische Mikrobiologie (SYNMIKRO)
AG Quantitative und Computergestützte Mikrobiologie
Hans-Meerweinstraße 6
35043 Marburg/Lahn
Tel.: +49-(0)6421-2822582
Fax.: +49-(0)6421-2824430
georg.fritz(at)synmikro.uni-marburg.de
Homepage Link
Co-workers:
- Philipp Popp (TU Dresden)
- Anika Thorhauer (SYNMIKRO)
References:
Mascher
Höfler, C., Heckmann, J., Fritsch, A., Popp, P., Gebhard, S., Fritz, G. and Mascher, T. (2015) Cannibalism Stress Response in Bacillus subtilis. Microbiology (Reading, Engl.).
Fritz, G., Dintner, S., Treichel, N. S., Radeck, J., Gerland, U., Mascher, T. and Gebhard, S. (2015) A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism. MBio, 6, e00975.
Fritz, G. and Mascher, T. (2014) A balancing act times two: sensing and regulating cell envelope homeostasis in Bacillus subtilis. Mol. Microbiol., 94, 1201-1207.
Domínguez-Escobar, J., Wolf, D., Fritz, G., Höfler, C., Wedlich-Söldner, R. and Mascher, T. (2014) Subcellular localization, interactions and dynamics of the phage-shock protein-like Lia response in Bacillus subtilis. Mol. Microbiol., 92, 716-732.
Kesel, S., Mader, A., Höfler, C., Mascher, T. and Leisner, M. (2013) Immediate and Heterogeneous Response of the LiaFSR Two-Component System of Bacillus subtilis to the Peptide Antibiotic Bacitracin. PLoS ONE, 8, e53457.
Wolf, D., Kalamorz, F., Wecke, T., Juszczak, A., Mäder, U., Homuth, G., Jordan, S., Kirstein, J., Hoppert, M., Voigt, B., Hecker, M. and Mascher, T. (2010) In-depth profiling of the LiaR response of Bacillus subtilis. J. Bacteriol., 192, 4680-4693.
Rietkötter, E., Hoyer, D. and Mascher, T. (2008) Bacitracin sensing in Bacillus subtilis. Mol. Microbiol., 68, 768-785.
Jordan, S., Rietkötter, E., Strauch, M. A., Kalamorz, F., Butcher, B. G., Helmann, J. D. and Mascher, T. (2007) LiaRS-dependent gene expression is embedded in transition state regulation in Bacillus subtilis. Microbiology (Reading, Engl.), 153, 2530-2540.
Jordan, S., Junker, A., Helmann, J. D. and Mascher, T. (2006) Regulation of LiaRS-dependent gene expression in Bacillus subtilis: identification of inhibitor proteins, regulator binding sites, and target genes of a conserved cell envelope stress-sensing two-component system. J. Bacteriol., 188, 5153-5166.
Mascher, T., Zimmer, S. L., Smith, T.-A. and Helmann, J. D. (2004) Antibiotic-inducible promoter regulated by the cell envelope stress-sensing two-component system LiaRS of Bacillus subtilis. Antimicrob. Agents Chemother., 48, 2888-2896.
Mascher, T., Margulis, N. G., Wang, T., Ye, R. W. and Helmann, J. D. (2003) Cell wall stress responses in Bacillus subtilis: the regulatory network of the bacitracin stimulon. Mol. Microbiol., 50, 1591-1604.
Fritz
Höfler, C., Heckmann, J., Fritsch, A., Popp, P., Gebhard, S., Fritz, G. and Mascher, T. (2015) Cannibalism Stress Response in Bacillus subtilis. Microbiology (Reading, Engl.).
Fritz, G., Dintner, S., Treichel, N. S., Radeck, J., Gerland, U., Mascher, T. and Gebhard, S. (2015) A New Way of Sensing: Need-Based Activation of Antibiotic Resistance by a Flux-Sensing Mechanism. MBio, 6, e00975.
Fritz, G. and Mascher, T. (2014) A balancing act times two: sensing and regulating cell envelope homeostasis in Bacillus subtilis. Mol. Microbiol., 94, 1201-1207.
Fritz, G., Megerle, J. A., Westermayer, S. A., Brick, D., Heermann, R., Jung, K., Rädler, J. O. and Gerland, U. (2014) Single cell kinetics of phenotypic switching in the arabinose utilization system of E. coli. PLoS ONE, 9, e89532.
Domínguez-Escobar, J., Wolf, D., Fritz, G., Höfler, C., Wedlich-Söldner, R. and Mascher, T. (2014) Subcellular localization, interactions and dynamics of the phage-shock protein-like Lia response in Bacillus subtilis. Mol. Microbiol., 92, 716-732.
Megerle, J. A., Fritz, G., Gerland, U., Jung, K. and Rädler, J. O. (2008) Timing and dynamics of single cell gene expression in the arabinose utilization system. Biophys. J., 95, 2103-2115.