Gene regulatory networks

Regulation of iron homeostasis

Iron is an essential but often growth-limiting micronutrient due to the low solubility of Fe³⁺, requiring tightly regulated uptake and storage systems to prevent toxicity. We study the gene regulatory networks and signalling pathways controlling iron and heme homeostasis in the Gram-positive soil bacterium Corynebacterium glutamicum. Using defined microbial communities, we investigate how heme- and siderophore-mediated interactions shape community dynamics. Our approach combines classical molecular microbiology with genome-wide profiling (ChIP-seq), omics technologies (RNA-seq), and mathematical modelling.

Xenogeneic silencing

The discrimination between ‘self’ and ‘foreign’ represents a key feature of the bacterial immune system. Besides small molecule-mediated defenses, we study the function and diversity of xenogeneic silencing (XS) proteins. XS proteins, such as the actinobacterial Lsr2-like proteins, can recognize foreign DNA elements by binding to AT-rich DNA regions. These proteins play an important role in the acquisition of novel genetic information and facilitate the evolution of regulatory networks. We recently identified a prophage-encoded Lsr2-like xenogeneic silencing protein playing a key role in the silencing of cryptic prophage islands and for the maintenance of the lysogenic state. Insights are harnessed for the development of novel expression systems or metabolic toggle switches.

Selected publications

1. Wiechert, J., Badia Roige, B., Dohmen-Olma, D., Hindra, Zhang, X., Stella, R. G., Elliot, M. A., & Frunzke, J. (2025). CRISPR/dCas-mediated counter-silencing: reprogramming dCas proteins into antagonists of xenogeneic silencers. mBio, 16, e0038225. DOI: 10.1128/mbio.00382-25
2. Krüger A, Weber U, Frunzke J (2025). Genome-Wide Analysis of DtxR and HrrA Regulons Reveals Novel Targets and a High Level of Interconnectivity Between Iron and Heme Regulatory Networks in Corynebacterium glutamicum. Mol Microbiol. 2025 Aug;124(2):115-130. doi: 10.1111/mmi.15376.
3. Krüger A, Keppel M, Sharma V, Frunzke J (2022) The diversity of heme sensor systems - heme-responsive transcriptional regulation mediated by transient heme protein interactions. FEMS Microbiol. Rev. 10.1093/femsre/fuac002.
4. Wiechert J, Filipchyk A, Hünnefeld M, Gätgens C, Brehm J, Heermann R and Frunzke J, (2020) Deciphering the Rules Underlying Xenogeneic Silencing and Counter-Silencing of Lsr2-like Proteins Using CgpS of Corynebacterium glutamicum as a Model. mBio, doi: 10.1128/mBio.02273-19
5. Keppel M, Hünnefeld M, Filipchyk A, Viets U, Davoudi C-F, Krüger A, Mack C, Pfeifer E, Polen T, Baumgart M, Bott M, and Frunzke J (2020) HrrSA orchestrates a systemic response to heme and determines prioritization of terminal cytochrome oxidase expression. Nucleic Acids Res, doi: 10.1093/nar/gkaa415
6. Pfeifer E, Hünnefeld M, Popa O, Polen T, Kohlheyer D, Baumgart M, and Frunzke J (2016) Silencing of cryptic prophages in Corynebacterium glutamicum. Nucleic Acids Res, doi: 10.1093/nar/gkw692sdf

Funding