Forskning ved Københavns Universitet - Københavns Universitet

Kenn Gerdes
Kenn Gerdes

 Current Collaborators

  • Boris Macek, University of Tübingen, Germany
  • Gert Bange, SYNMIKRO, Marburg, Germany
  • Ramesh Wigneshweraraj, ICL, London, UK
  • Ditlev Brodersen, Aarhus University, DK
  • Nick Thomson, Sanger Institute, UK
  • Chris Tang, Sir Willium Dunn School of Pathology, Oxford University, UK
  • Dominique Schneider, CNRS, Grenoble, France 
  • Emmannuelle Charpentier, MPI for Infection Biology, Berlin, Germany



The overarching research themes in the Gerdes group are Bacterial Stress Responses and Antibiotic Multidrug Tolerance (Persistence). Research within these fields facilitated the establishment of a Research Centre of Excellence funded by the Danish National Research Foundation and the Novo Nordisk Foundation. The Centre is called Bacterial Stress Responses and Persistence (BASP). Most bacteria live in constantly changing environments and have evolved highly efficient resistance mechanisms that allow them to withstand stressful conditions. For their survival in the environment or during infections, almost all bacteria depend on the ubiquitous regulatory molecules tetra and penta-guanosine phosphate, collectively called (p)ppGpp or Magic Spots. Thus, the (p)ppGpp-dependent stress response is required for almost all pathogenic bacteria to be virulent. Our basic research aims to unravel bacterial survival and virulence mechanisms and how these mechanisms contribute to antibiotic persistence.

Magic Spots were originally discovered during experiments with the model organism E. coli undergoing amino acid starvation. These analyses led to the early definition of the “stringent response” during which (p)ppGpp rapidly increases to high levels and reprograms cellular metabolism from rapid to slow growth or dormancy. Magic spots profoundly influence gene expression allowing the bacteria to survive during limited nutrient supply and under many other adverse conditions. Importantly, rRNA synthesis is severely curtailed while transcription of amino acid biosynthetic operons is stimulated. Thus, a primary role of (p)ppGpp is to adjust cell growth to the available nutrient resources. However, (p)ppGpp affects many other cellular processes, such as replication, transcription and protein turnover, either directly or indirectly. Importantly, even though (p)ppGpp has been known for almost  50 years, it is not yet understood how its synthesis is controlled. In E. coli, Magic Spots are synthesized and hydrolyzed by the bifunctional Rel enzymes RelA and SpoT that are regulated by a number of factors including ribosome-bound tRNA and essential GTPases. However, at the molecular level, surprisingly little is known as to how Rel enzymes are regulated. As described further below, a long-term goal of our research is to understand how the enzymatic activities of RelA and SpoT are regulated and how (p)ppGpp contributes to bacterial virulence and persistence (multidrug tolerance). Research on the almost ubiquitous regulatory molecule (p)ppGpp has recently undergone a revival and the modern definition of the stringent response encompasses the cellular changes elicited by (p)ppGpp in all relevant bacteria, including major pathogens.


The Stringent Response and Other Survival Mechanisms (Yong Zhang, Anurag Sinha, Thomas Prossliner)

  • RelA [(p)ppGpp Synthetase I]. We use UV-cross-linking and high-throughput sequencing of RNA (CRAC) to map the interactions between RelA, tRNA and ribosomal RNA to understand the molecular mechanism underlying activation of RelA. 
  • Translation-factors Induced in Stationary Phase. We wish to understand how the stationary-phase induced translation-factors RMF, HPF, RaiA and RsfS help bacteria survive during stationary phase

Transcriptional Control of spoT (Emilie Søndberg)

  • Using gene library screenings, several activators of spoT were discovered. For example, the competence regulon activator Sxy triggers spoT transcription by a CRP-cAMP dependent mechanism. We aim to understand the underlying molecular mechanism and physiological connections

Bacterial Persistence (Cinzia Fino)

  • Analysis of stochastic choices at the single cell level using multiple reporter systems in parallel
  • Identification of novel persister genes using saturated transposon mutagenesis and high throughput sequencing

Toxin – Antitoxins (Stine Vang Nielsen)

  • Analysis of TA-encoded toxins. Using phylogeny, we analyze the cellular targets of remotely related toxins
  • Regulation of hicAB loci. The hicAB locus of E. coli is regulated transcriptionally and translationally by several factors. We aim to understand the underlying physiological induction mechanisms
  • Analysis of hipBA regulation at the transcriptional and translational levels
  • Identification of a novel TA gene families
  • TAs and persistence

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