Dormancy as bacterial survival strategy
The group has a strong interest in the events that lead to persister cell formation in the model bacterium Escherichia coli. Persisters are transiently multidrug-tolerant cells that have entered a dormant state and thereby escape antibiotic treatments. As soon as they resuscitate from dormancy, they are fully susceptible to antibiotics again. We aim to unravel the physiological state of persister cells and the mechanisms leading to persistence. We apply microbiological, genetic, and biochemical tools, and use high-throughput techniques for investigation of bacterial transcriptomes and proteomes.
Toxin-antitoxin systems and persister formation
The type I toxin-antitoxin system tisB/istR-1 is studied as a model system for toxin-induced dormancy. Toxin TisB is a small hydrophobic protein with a length of 29 amino acid residues and causes depolarization of the inner membrane. The concomitant ATP depletion inhibits growth and favors persister formation. We are interested in TisB functionality and how regulation of tisB contributes to persistence.
Effects of membrane depolarization on persister physiology
Toxin-induced depolarization of the inner membrane has a profound impact on cell physiology, including ATP depletion and perturbation of membrane functioning. We aim to unravel how depolarization shapes the physiology of bacterial persister cells.
Investigation of the persister cycle
Persister cells eventually awake and resume growth. We aim to identify factors that are crucial for awakening and recovery from the persister state. Understanding how bacteria resuscitate from the persister state might contribute to an improved treatment of chronical infections that are regularly caused by persister cells.
Berghoff BA (2021) Analyzing Persister Proteomes with SILAC and Label-Free Methods. Methods Mol Biol 2357: 149-159.
Edelmann D, Leinberger FH, Schmid NE, Oberpaul M, Schäberle TF, Berghoff BA (2021) Elevated Expression of Toxin TisB Protects Persister Cells against Ciprofloxacin but Enhances Susceptibility to Mitomycin C. Microorganisms 9: 943.
Edelmann D, Oberpaul M, Schäberle TF, Berghoff BA (2021) Post-transcriptional deregulation of the tisB/istR-1 toxin-antitoxin system promotes SOS-independent persister formation in Escherichia coli. Environ Microbiol Rep 13: 159-168
Berghoff BA, Wagner EGH (2019) Persister formation driven by TisB-dependent membrane depolarization. In: Persister Cells and Infectious Disease; Lewis K (Ed.), Springer International Publishing.
(2019) Type I toxin-dependent generation of superoxide affects the persister life cycle of Escherichia coli. Sci Rep 9: 14256.
(2019) High-Throughput Proteomics Identifies Proteins With Importance to Postantibiotic Recovery in Depolarized Persister Cells. Front. Microbiol 10: 378
Synthetic small RNAs as tool for gene regulation
Small RNAs (sRNAs) are versatile regulators in prokaryotes. In most cases, sRNAs consist of distinct modules, such as seed regions, binding sites for RNA-binding proteins, and Rho-independent terminator hairpins. Synthetic biology approaches will be used to recombine these modules and construct (semi-) synthetic sRNAs for gene regulation in bacteria. We will explore the potential of these synthetic sRNAs to control complex phenotypic traits, such as bacterial persistence and antibiotic resistance.