Bacterial Cell Cycle Group - Anders Løbner-Olesen Group

The group has historically worked on cell cycle control of DNA replication in bacteria, with focus on Escherichia coli. This remains one of the focus areas of the lab.

We have described key aspects of the E. coli cell cycle control including the DnaA protein being limiting for replication, the role of Dam, and the importance of cis-acting control regions. Recently we have widened our focus to include the development of antimicrobials with special emphasis on antimicrobial peptides.

 

 

Antimicrobial Drug Discovery and Development

Vinoth Wigneswaran
We are interested in the discovery of new antimicrobials. Specifically we are involved in the development of novel antimicrobial peptides targeting highly drug-resistant Gram-negative bacteria (E. coli, K. pneumonia, A. baumannii and P. aeruginosa). We have previously described a new antimicrobial peptide in our lab that shows promising antimicrobial activity and we are currently in the process of characterizing this compound. This includes description of mechanism of action, analysis of antimicrobial effect on synthesis of macromolecules (peptidoglycan, protein, DNA, RNA), resistance development and effect of cellular physiology. This also includes routine testing of minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and combinatorial testing for collateral sensitivity through synergy of antimicrobials. Furthermore, we are interested in the mechanisms involved in resistance development towards antimicrobial peptides such as colistin. These resistance mechanisms usually involve modification to the bacterial membrane, such as the addition of phosphoethanolamine and aminoarabinose to the lipopolysaccharide (LPS), which changes the membrane properties. We apply genetic manipulation, genome engineering and mass spectrometry to elucidate how these changes influence antibacterial efficacy and how these alterations may lead to collateral sensitivity, new target discovery and treatment possibilities.


Engineering biological memory in bacteria

 Godefroid Charbon

The goal is to develop a new tool for information storage in bacteria using DNA methylation as an epigenetic switch. We are developing an artificial gene promoter regulated by methylation to create specific DNA methylation profiles. The novel DNA methylation patterns generated will be used to memorize inputs in living bacteria. Here we wish to design a DNA methylation system to track and record DNA replication to identify and study metabolically dormant bacteria. This system will be usable for studying bacterial phenotypic heterogeneity.


Novel antimicrobial peptide discovery

Anna Elisabeth Ebbensgaard
In response to the increasing worldwide threat to human health posed by the emergence of bacterial resistance to currently used antibiotics, the overall aim of the recently established “Center for Peptide Antibiotics” (CEPAN) is to establish a discovery platform for peptide-based antibiotics against bacterial pathogens. In particular, we are interested in the discovery of new antimicrobial peptides and identification of novel targets for peptide and PNA (peptide nucleic acid) based peptides, as well as in the discovery of bacterial envelope permeabilizing peptides (EPPs). We use intracellular peptide display to identify novel hit peptides as well as novel targets for antibiotics. Coupling intracellular peptide display to either deep sequencing or more traditional bioactivity assays, we aim to identify novel bioactive peptides targeting bacterial pathogens.

 

Frimodt-Møller, J., Campion, C., Nielsen,P.E., and Løbner-Olesen, A. 2021. Translocation of non-lytic antimicrobial peptides and bacteria penetrating peptides across the inner membrane of the bacterial envelope, Current Genetics, https://doi.org/10.1007/s00294-021-01217-9

Campion, C., Charbon, G., Thosen, T.T., Nielsen, P.E., and Løbner-Olesen, A. 2021. Antisense inhibition of the Escherichia coli NrdAB aerobic ribonucleotide reductase is bactericidal due to induction of DNA strand breaks. J. Antimicrob. Chemother., doi:10.1093/jac/dkab305

Frimodt-Møller, J., Boesen, T.O., Charbon, G., and Løbner-Olesen, A. 2021. Bacterial chromosomes and their replication. Molecular Medical Microbiology 3rd Ed. Edited by: Tang, Y.-W., Zhang, J.-R., Liu, D., Sails, A.D., Hindiyeh, M., and Spearman, P. Academic Press, Elsevier, Chapter 14, In press

Charbon, G., Frimodt‑Møller, J., and Løbner‑Olesen, A. 2021. Arresting coli chromosome replication upon energy starvation in Escherichia, Current Genetics, ttps://doi.org/10.1007/s00294-021-01202-2

Pereira, W., Pereira, C., Assunção, R., da Silva, I., Rego, F., Alves, L., Santos, J., Nogueira, F., Zagmignan, A., Thomsen, T., Løbner-Olesen, A., Krogfelt, K., da Silva, L., and  Abreu, A. 2021. New Insights into the Antimicrobial Action of Cinnamaldehyde towards Escherichia coli and Its Effects on Intestinal Colonization of Mice. Biomolecules 2021, 11, 302, https://doi.org/10.3390/biom11020302.

Charbon, G.S., Chamizo, B.M., Campion, C.,  Li, X., Jensen, P.R., Frimodt-Møller, J.,  and Løbner-Olesen, A. 2021. Energy Starvation Induces a Cell Cycle Arrest in Escherichia coli by Triggering Degradation of the DnaA Initiator Protein.  Frontiers in Molecular Biosciences, 8, 629953, doi: 10.3389/fmolb.2021.6299538

Ebbensgaard, A., Løbner-Olesen, A., and Frimodt-Møller, J. 2020. The role of efflux pumps in the transition from low-level to clinical antibiotic resistance. Antibiotics, 9, 855. doi: 10.3390/antibiotics9120855

Frimodt-Møller, J., Koulouktsis, A., Charbon, G.S., Otterlei, M., Nielsen, P.E. and Løbner-Olesen, A. 2021. Activation of the Cpx-envelope stress response system promotes tolerance to antibacterials delivered by arginine-rich peptides and aminoglycosides in Escherichia coli. Molecular Therapy: Nucleic Acid, doi: https://doi.org/10.1016/j.omtn.2021.06.009

Sinha, A.K., Løbner-Olesen, A. and Riber, L. 2020. Bacterial Chromosome Replication and DNA Repair During the Stringent Response. Front. Microbiol., 11, 582113. doi: 10.3389/fmicb.2020.582113

Jensen, S.K., Thomsen, T.T., Oddo, A., Franzyk, H., Løbner-Olesen, A. and Hansen, P.R. 2020. Novel Cyclic Lipopeptide Antibiotics: Effects of Acyl Chain Length and Position. Int. J. Mol. Sci. 21, E5829. doi: 10.3390/ijms21165829. PMID: 32823798

 

 

Center for Peptide-Based Antibiotics: Peptide Antibiotics against Resistant Bacterial Infections

Agency: Novo Nordisk Challenge program
Main applicant: Prof. Peter E. Nielsen, University of Copenhagen, Denmark
Co-applicant: Anders Løbner-Olesens (shared) 
Expiration date: 2022
Link: https://cepan.ku.dk/


IRPD: A Novel in vivo Peptide Display Technology in Bacteria

Agency: Lundbeck Experiment Programme
Main applicant: Anna Ebbensgaard
Expiration date: 2023 


Engineering biological memory in bacteria

Agency: VILLUM Experiment Programme
Main applicant: Anders Løbner-Olesen (shared) 
Expiration date: 2022


Insane in the membrane; how to avoid crowding of the Eschericia coli inner membrane?

Agency: VILLUM Experiment Programme
Main applicant: Jakob Frimodt-Møller 
Expiration date: 2022 

 

 

For public relations or our public outreach program, please contact Jakob Frimodt-Møller

 

 

Researchers

Name Title Phone E-mail
Amalie Shanthi Tripax Laboratory Technician   E-mail
Anders Løbner-Olesen Professor +4535322068 E-mail
Anna Elisabeth Ebbensgaard Assistant Professor +4535336946 E-mail
Elisabeth Dohmann Chang Postdoc +4535336230 E-mail
Godefroid Charbon Associate Professor +4535322098 E-mail
Irene Martínez Román Guest Researcher   E-mail
Jakob Frimodt-Møller Postdoc   E-mail
Thias Oberg Boesen PhD Fellow +4520313984 E-mail

Other members

Name Title E-mail
Christopher Campion PhD fellow  E-mail
Meiqin Zhang External PhD fellow E-mail
Andreas Mariboe Russel                                       MSc student E-mail
Alaa Ismail Hassan                                                  MSc student E-mail
Shad Al Mousawi                                                     MSc student E-mail
Olga Tugwell                                                             MSc student E-mail
Kine Sander Noreng                                               MSc student E-mail
Qi Wang                                                                      MSc student E-mail
Mia Arris Nielsen                                                     External MSc student E-mail
Rikke Overgaard Kiilerich                                      External MSc student E-mail

Contact

Professor Anders Løbner-Olesen
Functional Genomics
Office: 4.2.15
Ole Maaløes Vej 5
DK-2200 Copenhagen N

Email: lobner@bio.ku.dk
Phone: +45 35 32 20 68
Mobile: +45 51 43 03 26

ORCID: 0000-0002-0344-6417