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Bacteria as single living organisms are exposed to rapidly changing external conditions. Given strong selection pressure, it is not surprising that bacteria have evolved sophisticated signaling systems to constantly monitor changes in external parameters, such as acidity, nutrients, eukaryotic signals and to adapt their structure, physiology and behavior accordingly.

Research in Kirsten Jung's lab focuses on elucidating the molecular mechanisms of stimulus perception under acid stress in Escherichia coli and other γ-proteobacteria (Area 1). We study the uptake, excretion and homeostasis of primary metabolites, such as pyruvate, in Escherichia, Salmonella and Vibrio (Area 2). In a new project we elucidate the role of mRNA modifications during abiotic and biotic stress response in Escherichia and Vibrio (Area 3). We also investigate translation elongation factor P (EF-P), a protein that alleviates ribosome stalling at polyproline stretches, and its post-translational modification systems (Area 4). Last but not least, we are working on identifying new intracellular targets of natural compounds (Area 5).


Research Area 1: Acid stress sensing in Escherichia coli and other γ-proteobacteria

Acid resistance is an important property of many bacteria to survive in acidic environments like the human gastrointestinal tract. E. coli, for example, has several sophisticated signaling systems to sense and appropriately respond to environmental acid stress by regulating the activity of five inducible acid resistance systems. One of these systems is the Cad system that is only induced under moderate acidic stress in a lysine-rich environment by the pH-responsive transcriptional regulator CadC. We study the localization and spatiotemporal dynamics of CadC and other membrane-integrated and intracellular receptors involved in acid stress response in Escherichia and Vibrio species with a specific focus on their DNA surface exploration during target search.

               the localization of the one-component receptor

Figure 1: The localization of the one-component receptor CadC, an acid stress sensor, is directed by binding to DNA within Escherichia coli cells.

Recently, we have gained first evidence that an acidification of the cytoplasm of Escherichia coli is used as stimulus to activate regulatory processes that contribute to acid stress resistance. Our goal now is to identify and characterize the transcriptional regulators that are activated at the low pH of the cytoplasm.

                                                     The molecular design of the Cad-system

Figure 2: The molecular design of the Cad-system influences the degree of noise in CadB-eGFP abundance under acid stress.

Selected Publications:

  • Martini, L., Brameyer, S., Hoyer. E., Jung. K.*, Gerland, U.* (2021) Dynamics of chromosomal target search by a membrane-integrated one-component receptor. PloS Comp. Biol., 17: e1008680.
  • Brameyer, S., Hoyer, E., Bibinger, S., Burdack, K., Lassak, J., Jung, K. (2020) Molecular design of a signaling system influences noise in protein abundance under acid stress in different gamma-proteobacteria. J Bacteriol, 202 (16): e00121-20.
  • Brameyer, S., Rösch, T.C., Andarib, J.A., Hoyer, E., Schwarz, J., Graumann, P.L., Jung, K. (2019) DNA-binding directs the localization of a membrane-integrated receptor of the ToxR family. Commun. Biol., 2: 4.
  • Buchner, S., Schlundt, A., Lassak, J., Sattler, J., Jung, K. (2015) The role of a disordered linker in the pH-sensor CadC of Escherichia coli, J. Mol. Biol., 427(15): 2548-2561.
  • Lorenz, N., Shin, J.Y., Jung, K. (2017) Activity, abundance and localization of quorum sensing receptors in Vibrio harveyi, Front. Microbiol., 8: 634.
  • Fritz, G., Koller, C., Tetsch, L., Haneburger, I., Burdack, K., Jung, K., Gerland, U. (2009) Induction kinetics and feedback inhibition of a conditional stress response system in Escherichia coli, J. Mol. Biol. 393: 272–286.top

Research Area 2: Molecular mechanisms of stimulus perception by histidine kinase/response regulator systems and regulation of uptake and excretion of primary metabolites

Bacteria sense and respond to various stress conditions by employing so called two-component systems. These systems consist of a histidine kinase and a response regulator, which sense environmental stimuli, transduce information via phosphorylation and induce a cellular response. Escherichia coli, for example, contains 32 of these systems.
We are studying how sensing and uptake of the primary metabolite pyruvate is coordinated by the BtsS/BtsR and YpdA/YpdB histidine kinase systems in Escherichia, Vibrio and Salmonella species. The studies focus on the investigation of the unusual signal transduction within the pyruvate-sensing histidine kinase/response regulator systems,as well as on uptake and excretion of this metabolite.

                                         Model of the nutrient sensing

Figure 3: Model of the nutrient sensing BtsS/BtsR-YpdA/YpdB network in E. coli.

Selected Publications:

  • Göing, S., Gasperotti, A.F., Yang, Q., Defoirdt, T., Jung, K. (2021) Insights into a pyruvate sensing and uptake system in Vibrio campbellii and its importance for virulence. J. Bacteriol. 203: e00296-21
  • Steiner, B.D., Eberly, A.R., Hurst, M.N., Zhang, E., Behr, S., Jung, K., Hadjifrangiskou, M. (2018) Evidence of cross-regulation in two closely-related pyruvate-sensing systems in uropathogenic Escherichia coli, J. Membr. Biol., 251(1):65-74.
  • Vilhena, C., Kaganovitch, E., Shin, J.Y., Grünberger, A., Behr, S., Kristoficova, I., Brameyer, S., Kohlheyer, D., Jung, K. (2018) A single cell view of the BtsSR/YpdAB pyruvate sensing network in Escherichia coli and its biological relevance, J. Bacteriol., 200: e00536-17.
  • Behr, S., Kristoficova, I., Wittig, M., Breland, E.J., Eberly, A.R., Sachs, C., Schmitt-Kopplin, P., Hadjifrangiskou, M., Jung, K. (2017) Identification of a high-affinity pyruvate receptor in Escherichia coli, Sci. Rep., 7: 1388.
  • Fried, L., Behr, S., Jung, K. (2013) Identification of a target gene and activating stimulus for the YpdA/YpdB histidine kinase/response regulator system in Escherichia coli, J. Bacteriol. 195: 807-815
  • Kraxenberger, T., Fried, L., Behr, S., Jung, K. (2012) First insights into the unexplored two-component system YehU/YehT in Escherichia coli, J. Bacteriol. 194: 4272-4284.top

Research Area 3: The role of m6A-mRNA modification to control stress response and phage replication

In this project we study the role of mRNA modifications to control stress response in E. coli and phage replication in the marine bacterium Vibrio campbellii ATCC BAA-116, a model organism for quorum sensing.

The role of mRNA modification in bacteria

Figure 4: The role of mRNA modification in bacteria

Selected Publications:

  • Petrov, D.P., Kaiser, S., Kaiser, S.*, Jung, K.* (2021) Quantitative profiling and dynamics of mRNA modifications in Escherichia coli. ChemRxiv. Cambridge: Cambridge Open Engage, https://doi.org/10.26434/chemrxiv-2021-0wc9g
  • Reichle, V., Petrov, D., Weber, V., Jung, K., Kellner, S. (2019) NAIL-MS reveals the repair of 2-methylthiocytidine by AlkB in E. coli. Nat. Commun., 10: 5600.


Research Area 4: Post-translational modifications of elongation factor P (EF-P) and the role of poly-proline motifs

The fundamental process of protein synthesis is catalyzed on ribosomes. We have recently demonstrated that bacterial ribosomes become arrested when translating proteins contain consecutive polyproline stretches, and that this arrest is alleviated by the translation elongation factor EF-P. Furthermore, we could show that the post-translational β-lysinylation of lysine34 of Escherichia coli EF-P by the enzymes EpmA and EpmB and the rhamnosylation of arginine32 of Shewanella EF-P by EarP, respectively, are critical for the rescue activity of EF-P. EF-P is aminopentanoylated in Bacillus and other members of the Firmicutes. In contrast, the EF-Ps of Actinobacteria – specifically, Clostridium glutamicum, Streptomyces coelicolor and Mycobacterium tuberculosis – alleviate ribosome stalling at polyproline motifs without the need for any activating post-translational modification.

                                                Ef-P prevents ribosome stalling                                 

Figure 5: EF-P prevents ribosome stalling at polyproline stretches.

Many virulence factors contain polyproline stretches, which explains why modified EF-P is critical for bacterial pathogenicity. Polyproline motifs are required for the regulation of copy number or dimerization or catalytic activity of certain proteins. The project focuses on the elucidation and characterization of synthetic and novel post-translational modification pathways of EF-P.

Selected Publications:

  • Pinheiro, B., Scheidler, C.M., Kielkowski, P., Schmid, M., Forné, I., Ye, S., Reiling, N., Takano, E., Imhof, A., Sieber, S. A., Schneider, S., Jung, K. (2020) Structure and function of a novel elongation factor P subfamily in Actinobacteria. Cell Rep., 30: 4332-4342.e5.
  • Pfab, M., Kielkowski, P., Krafczyk, R., Volkwein, W., Sieber, S.A., Lassak, J., Jung, K. (2021) Synthetic post-translational modifications of elongation factor P using the ligase EpmA. FEBS J., 288: 663-677.
  • Motz, L., Jung, K. (2018) The role of polyproline motifs in the histidine kinase EnvZ, PLoS One, 13(6): e0199782.
  • Qi, F., Motz, M., Jung, K., Lassak, J. and Frishman, D. (2018) Evolutionary analysis of polyproline motifs in Escherichia coli reveals their regulatory role in translation, PLoS Comp. Biol. 14(2):e1005987.
  • Starosta, A.L., Lassak, J., Atkinson, G.C., Peil, L., Woolstenhulme, C.J., Virumäe, K., Buskirk, A., Tenson, T., Remme, J., Jung, K., Wilson, D.N. (2014) A conserved proline triplet in Val-tRNA synthetase and the origin of elongation factor P, Cell Rep., 9: 476-483.
  • Lassak, J., Keilhauer, E., Fürst, M., Wuichet, K., Gödeke, J., Starosta, A.L., Chen, J., Søgaard-Andersen, L., Rohr, J., Wilson, D.N., Häussler, S., Mann, M., Jung, K. (2015) Arginine-rhamnosylation as new strategy for post-translational modification of translation elongation factor P, Nat. Chem. Biol., 11: 266-70, doi:10.1038/nchembio.1751.
  • Ude, S., Lassak, J., Starosta, A. L., Kraxenberger, T., Wilson, D.N., Jung, K. (2013) Translation elongation factor EF-P alleviates ribosome stalling at polyproline stretches. Science, 339: 82-85.


Research Area 5: Chemical Biology and the identification of protein targets of natural compounds

There are about 500,000 molecules in the communication between pro- and eukaryotes. We use bacterial model organisms to study the effect of natural compounds such as fimbrolides, quorum quenchers or eukaryotic hormones on the phenotypic behavior of bacteria, such as quorum sensing and chemotaxis. The project also focuses on the identification of the cellular targets of these compounds.

Chemical communication 

Figure 6: Chemical communication between pro- and eukaryotes.

Selected Publications:

  • Weigert Muñoz, A., Hoyer, E., Schumacher, K., Grognot, M., Taute, K., Hacker, S., Sieber, S.A.*, Jung, K.* (2021) Eukaryotic catecholamine hormones influence the chemotactic control of Vibrio campbellii by binding to the coupling protein CheW, ChemRxiv. Cambridge: Cambridge Open Engage; https://doi.org/10.33774/chemrxiv-2021-gx4mr
  • Rauh, T., Brameyer, S., Itzen, A., Kielkowski, P., Jung, K., Sieber, S.A. (2020) MS-based in situ proteomics reveals AMPylation of host proteins during bacterial infection, ACS Infect. Dis., 6: 3277-3289.
  • Zhao, W., Lorenz, N., Jung, K., Sieber, S.A. (2016) Mechanistic analysis of aliphatic β-lactones in Vibrio harveyi reveals a quorum sensing independent mode of action, Chem. Commun., 52: 11971-11974
  • Zhao, W., Lorenz, N., Jung, K., Sieber, S.A. (2016) Fimbrolide natural products disrupt bioluminescence of Vibrio harveyi by targeting autoinducer biosynthesis and luciferase activity, Angew. Chem. Int. Ed. Engl. 55(3): 1187-91.
  • Rossmann, F.S., Wobser, D., Racek, T., Puchalka, J., Rabener, E.M., Reiger, M., Hendrickx, A.P.A., Diederich, A., Jung, K., Klein, C., Huebner, J. (2015) Phage-mediated dispersal of biofilm and distribution of bacterial virulence genes is induced by Quorum Sensing, PLoS Pathog., 11(2): e1004653.
  • Chu, Y., Nega, M., Wölfle, M., Plener, L., Grond, S., Jung, K., Götz, F. (2013) A new class of quorum quenching molecules from Staphylococcus species affects communication of Gram-negative bacteria, PLoS Pathog., 9(9): e1003654.