Research Areas

Antibiotics are stage center for the three groups of the Chair of General Microbiology. We cover a broad range of research topics: From antibiotic production, via development and spread of antibiotic resistance, to their role as signaling molecules in the context of stress responses and multicellular differentiation. Beyond basic research, we also develop molecular tools for antibiotic research and in the context of Synthetic Biology applications.

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Detailed description of our research areas

INTERACTION OF BACTERIA WITH THEIR ENVIRONMENT

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ANTIMICROBIAL RESISTANCES

The rapid spread of antibiotic resistance is considered as one of the most severe health threats of the 21st century (WHO, 2014). A comprehensive knowledge of the driving mechanisms is urgently needed if we do not want to be confronted with untreatable bacterial infections in the near future. Our overarching goal is to contribute to a better understanding of the evolution and spread of antibiotic resistance in the environment.

ANTIMICROBIAL STRESS SIGNALING AND RESPONSES

Two-component systems (2CSs) represent the most important bacterial signalling devices to connect an extracellular stimulus with a intracellular response. We study unusual 2CS that mediate resistance against cell wall antibiotics. Driving questions are: What is the mechanism of stimulus perception? How are related 2CSs insulated from one another to ensure regulatory specificity?

Summary of our research interests

We are interested in how Gram-positive bacteria communicate with, and respond to changes occurring within their environment. The information flow between a cell and its surrounding is called signal transduction. Our primary model organisms are Bacillus subtilis (Firmicutes: low G+C Gram-positive) and Streptomyces venezuelae (Actinobacteria: high G+C Gram-positive). In addition, we also study the biotechnological use of the nonconventional yeast Yarrowia lipolytica.

Our primary research focus is to identify and characterize signal transducing systems (two-component systems, TCSs, and extracytoplasmic function sigma factors, ECFs) involved in mediating bacterial stress responses with a special emphasize on HOW bacteria detect their input signal, i.e. the mechanism of stimulus perception. Moreover, we investigate the molecular basis for the specificity of interaction interfaces in bacterial signaling. A third central area of research is to understand how those systems are embedded in and wired within complex regulatory networks and global signaling cascades.

To gain such systems biology understanding, we combine approaches from comparative genomics, molecular genetics, and biochemistry, with single cell studies and mathematical modeling. This strategy was successfully used to characterize unusual TCSs involved in mediating antibiotic resistance. Moreover, we established ECFs as the third pillar of bacterial signal transduction and identified numerous novel mechanisms of ECF-dependent signal transduction.

Our work will ultimately allow us to re-design and deliberately re-wire regulatory systems. The resulting novel switches will be used to orchestrate complex expression programs in cell-based biofactories. Other Synthetic Biology projects focus on the development of standardized genetic tools for Bacillus subtilis and the use of their endospores as enzymatically functionalized microparticles.

Recent review articles:

Radeck J., Fritz G., and Mascher T. (2016) The cell envelope stress response of Bacillus subtilis: from static signaling devices to dynamic regulatory network. Curr. Genet. (Epub ahead of print)

Pinto D. and Mascher T. (2016) (Actino)Bacterial "intelligence": using comparative genomics to unravel the information processing capacities of microbes. Curr. Genet. (Epub ahead of print)

Wolf D. and Mascher T. (2016) The applied side of antimicrobial peptide-inducible promoters from Firmicutes bacteria: expression systems and whole-cell biosensors. Appl. Microbiol. Biotechnol. 100: 4817-29

Mascher T. (2014) Bacterial (intramembrane-sensing) histidine kinases: signal transfer rather than stimulus perception. Trends Microbiol. 22: 559-565

Mascher T. (2013) Signaling diversity and evolution of extracytoplasmic function (ECF) σ factors. Curr. Opin. Microbiol. 16:148-155

Wecke T. and Mascher T. (2011). Antibiotic research in the age of omics - from expression profiles to interspecies communication. J. Antimicrob. Chemother. 66:2689-704

Link to Publications