Bilde av Frøhlich, Christopher
Bilde av Frøhlich, Christopher
Young Investigator, Biochemistry and Enzyme Evolution Department of Pharmacy christopher.frohlich@uit.no 46968778 You can find me here

Christopher Frøhlich


Job description

Research Interests and Projects

As a researcher in the field of molecular biology, my primary interest lies in the intricate mechanisms of antimicrobial resistance (AMR), with a special focus on β-lactamases. My research journey, which began earnestly following the completion of my PhD, revolves around the evolution of these enzymes and their role in bacterial resistance.

Directed Evolution and Enzymology: One of my key interests is in directed evolution, a method that allows for the study of enzyme evolution in a controlled setting. This approach helps me understand how subtle genetic variations can lead to significant changes in enzyme activity and specificity, particularly in the context of antibiotic resistance. Additionally, my work in enzymology involves dissecting the kinetic and mechanistic aspects of β-lactamases, which is crucial for understanding how these enzymes confer resistance to β-lactam antibiotics.

Structural Investigations (X-ray Crystallography): Another significant aspect of my research is structural biology, specifically using X-ray crystallography. This technique provides a detailed view of the molecular structure of enzymes, allowing me to explore how structural changes in β-lactamases influence their function and interaction with antibiotics and inhibitors. These investigations are vital for designing effective inhibitors that can counteract antibiotic resistance.

Current and Future Projects: My current projects include exploring novel metallo-β-lactamase inhibitors, which are promising in the fight against carbapenem-resistant bacteria. In addition, by combining directed evolution, enzymology, and structural studies, I aim to develop a comprehensive understanding of these enzymes and design targeted strategies to mitigate their impact.

Current projects include:
a. Developing novel metallo-β-lactamase inhibitors.
b. Investigating β-lactamase-mediated resistance evolution.
c. Using directed evolution, enzymology, and structural analysis to explore enzyme adaptation in AMR.
d. Examining trade-offs in AMR evolution.


External Funding Awards:

12/2023 Young Investigator Grant, BATTLE: Antimicrobial resistance and Biofilm evolution (HelseNord)

02/2023 Marie Curie Awardee 


 Alumni

  • Marie Perruchot 
  • Elouan Ollivier 
  • Pascal Woschnitza 
  • Lilou Tronel 
  • Alexander Wessels 
  • Leon Przybyl
  • Anne Sofie Haukefer 
  • Nina Nevjar Martinsen

  • Alexandra Kondratieva, Katarzyna Palica, Christopher Frøhlich, Rebekka Rolfsnes Hovd, Hanna-Kirsti S. Leiros, Máté Erdélyi et al.:
    Fluorinated captopril analogues inhibit metallo-β-lactamases and facilitate structure determination of NDM-1 binding pose
    European Journal of Medicinal Chemistry 2024 ARKIV / DOI
  • Øyvind Myrvoll Lorentzen, Anne Sofie B. Haukefer, Pål Jarle Johnsen, Christopher Frøhlich :
    The Biofilm Lifestyle Shapes the Evolution of β-Lactamases
    Genome Biology and Evolution (GBE) 2024 ARKIV / DOI
  • Christopher Frøhlich, H. Adrian Bunzel, Karol Buda, Adrian J. Mulholland, Marc W. van der Kamp, Pål Jarle Johnsen et al.:
    Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase
    Nature Catalysis 2024 ARKIV / DOI
  • Yuwen Jia, Barbara Schroeder, Yvonne Pfeifer, Christopher Frøhlich, Lihua Deng, Christoph Arkona et al.:
    Kinetics, Thermodynamics, and Structural Effects of Quinoline-2-Carboxylates, Zinc-Binding Inhibitors of New Delhi Metallo-β-lactamase-1 Re-sensitizing Multidrug-Resistant Bacteria for Carbapenems
    Journal of Medicinal Chemistry 2023 DOI
  • Christopher Frøhlich, John Z Chen, Sevan Gholipour, Ayse N Erdogan, Nobuhiko Tokuriki :
    Evolution of β-lactamases and enzyme promiscuity
    Protein Engineering Design & Selection 2021 ARKIV / DOI
  • Christopher Frøhlich, João Alves Gama, Klaus Harms, Viivi H. A. Hirvonen, Bjarte Aarmo Lund, Marc W. van der Kamp et al.:
    Cryptic β-Lactamase Evolution Is Driven by Low β-Lactam Concentrations
    mSphere 2021 ARKIV / DOI
  • Ørjan Samuelsen, Ove Alexander Høgmoen Åstrand, Christopher Frøhlich, Adam Heikal, Susann Skagseth, Trine Josefine Olsen Carlsen et al.:
    ZN148 Is a Modular Synthetic Metallo-beta-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo
    Antimicrobial Agents and Chemotherapy 2020 ARKIV / DATA / DOI
  • Christopher Frøhlich, Vidar Sørum, Sandra Huber, Ørjan Samuelsen, Fanny Berglund, Erik Kristiansson et al.:
    Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1
    Journal of Antimicrobial Chemotherapy 2020 ARKIV / DOI
  • Zeeshan Muhammad, Susann Skagseth, Marc Boomgaren, Sundus Akhter, Christopher Frøhlich, Aya Ismael et al.:
    Structural studies of triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-β-lactamases
    Bioorganic & Medicinal Chemistry 01. August 2020 ARKIV / DOI
  • Anthony Prandina, Sylvie Radix, Marc Le Borgne, Lars Petter Jordheim, Zineb Bousfiha, Christopher Fröhlich et al.:
    Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitors
    Tetrahedron 2019 ARKIV / DOI
  • Geir Kildahl-Andersen, Christian Schnaars, Anthony Prandina, Sylvie Radix, Marc Le Borgne, Lars Petter Jordheim et al.:
    Synthesis and biological evaluation of zinc chelating compounds as metallo-β-lactamase inhibitors
    MedChemComm 2019 DOI
  • Christopher Frøhlich, Vidar Sørum, Ane Molden Thomassen, Pål Jarle Johnsen, Hanna-Kirsti S. Leiros, Ørjan Samuelsen :
    OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs
    mSphere 2019 ARKIV / DOI
  • Christian Schnaars, Geir kildahl-Andersen, Anthony Prandina, Roya Popal, Sylvie Radix, Marc Le Borgne et al.:
    Synthesis and preclinical evaluation of TPA-based zinc chelators as metallo-β-lactamase inhibitors
    ACS Infectious Diseases 2018 DOI
  • Christopher Frøhlich, Vidar Sørum, Nobuhiko Tokuriki, Pål Jarle Johnsen, Ørjan Samuelsen :
    Evolution of β-lactamase-mediated cefiderocol resistance
    Journal of Antimicrobial Chemotherapy 2011 ARKIV / DOI
  • Christopher Frøhlich :
    Naturens egen magi: Når 2+2 blir 12
    30. May 2024 DATA / FULLTEKST
  • Christopher Frøhlich :
    Divergent genetic evolution employs the same molecular mechanisms
    2024
  • Christopher Frøhlich, H. Adrian Bunzel, Karol Buda, Adrian J. Mulholland, Marc W. van der Kamp, Pål Jarle Johnsen et al.:
    Correction to: Epistasis arises from shifting the rate-limiting step during enzyme evolution of a β-lactamase (Nature Catalysis, (2024), 10.1038/s41929-024-01117-4)
    Nature Catalysis 2024 DOI
  • Øyvind Myrvoll Lorentzen, Christopher Fröhlich, Anne Sofie Haukefer, Sören Abel, Pål Jarle Johnsen :
    Evolution of Vibrio cholerae biofilms
    2023
  • Rebekka Rolfsnes Hovd, Pål Rongved, Ragnar Hovland, Åsmund Kaupang, Christopher Frøhlich, Sandra Huber et al.:
    Investigating the Mechanism of Action of a New Novel Dual β-Lactamase Inhibitor
    2023
  • Christopher Frøhlich, Adrian Bunzel, Karol Buda, Pål Jarle Johnsen, Nobuhiko Tokuriki :
    Divergent genetic evolution employs the same molecular mechanisms
    2023
  • Rebekka Rolfsnes Hovd, Pål Rongved, Ragnar Hovland, Åsmund Kaupang, Christopher Frøhlich, Sandra Huber et al.:
    Investigating the Mechanism of Action of a Novel Dual β-Lactamase Inhibitor
    2023
  • Christopher Frøhlich, Vidar Sørum, Nobuhiko Tokuriki, Ørjan Samuelsen :
    Evolution of ß-lactamase mediated cefiderocol resistance
    2022
  • Christopher Frøhlich, Adrian H. Bunzel, Marc W. Van Der Kamp, Adrian J. Mulholland, Hanna-Kirsti Schrøder Leiros, Pål Jarle Johnsen et al.:
    Positive epistasis drives the molecular evolution of the carbapenemase OXA-48
    2022
  • Christopher Frøhlich, Hanna-Kirsti S. Leiros :
    Vi må kanskje ta antibiotika hyppigere
    11. August 2022 DATA / PROSJEKT
  • Christopher Frøhlich, Hanna-Kirsti S. Leiros, Charlotte Miton, Nobuhiko Tokuriki :
    Ceftazidime drives the evolution of the carbapenemase OXA-48
    2020
  • Christopher Frøhlich, Hanna-Kirsti S. Leiros, Pål Jarle Johnsen, Ørjan Samuelsen :
    Sub-inhibitory concentrations of ceftazidime drive evolution of the OXA-48 carbapenemase
    2019
  • Christopher Frøhlich, Pål Jarle Johnsen, Hanna-Kirsti Schrøder Leiros, Ørjan Samuelsen :
    Evolution of OXA-48 under sub-MIC conditions
    2019
  • Christopher Frøhlich, Vidar Sørum, Hanna-Kirsti S. Leiros, Pål Jarle Johnsen, Ørjan Samuelsen :
    Development of OXA-48 mediated ceftazidme-avibactam resistance is associated with an evolutionary trade-off
    2018

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    Research interests

    First and last authorships (Updated 02/2014)

    *Corresponding authorships †Last authorships

    Lorentzen, M. Øyvind; Haukefer, Anne-Sofie; Johnsen, J. Pål, Fröhlich, Christopher (2024). The Biofilm Lifestyle Shapes the Evolution of β-Lactamase. Genome Biology and Evolution. doi: 10.1093/gbe/evae030*†

    Fröhlich, Christopher; Bunzel, H. A.; Buda, K.; Mullholland, L. A., Van der Kamp, W. M., Johnsen, P.J.; Leiros H.-K.S ;Tokuriki, Nobuhiko (2024). Epistasis Arises from Shifting the Rate-Limiting Step during Enzyme Evolution. Nature Catalysis. doi: 10.1038/s41929-024-01117-4. https://rdcu.be/dzqjk*

    Fröhlich, Christopher; Sørum, Vidar; Tokuriki, Nobuhiko; Johnsen, P.J.; Samuelsen, Ørjan (2022). Evolution of β-lactamase mediated cefiderocol resistance. Journal of Antimicrobial Chemotherapy. doi: 10.1093/jac/dkac221*

    Fröhlich, Christopher; Chen, J. Z; Gholipour, Sevan; Erdogan. (2021) A. N; Tokuriki, Nobuhiko. Evolution of β-lactamases and enzyme promiscuity. Protein Eng Des Sel.;34, 10.1093/protein/gzab013

    Fröhlich, Christopher; Gama J.A.; Harms K.; Hirvonen V.H.A.; Lund B.A.; van der Kamp M.W.; Johnsen P.J.; Samuelsen Ø. and Leiros H.-K.S. (2021) Cryptic β-lactamase evolution is driven by low β-lactam concentrations., mSphere, doi: 10.1101/2020.12.01.404343 *

    Fröhlich, Christopher; Sørum, Vidar; Huber, Sandra; Samuelsen, Ørjan; Berglund, Fanny; Kristiansson, Erik; Kotsakis, Stathis D.; Marathe, Nachiket P.; Larsson, Joakim; Leiros, Hanna-Kirsti S. (2020). Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1. Journal of Antimicrobial Chemotherapy. doi: doi:10.1093/jac/dkaa175.

    Fröhlich, Christopher; Sørum, Vidar; Thomassen, Ane Molden; Johnsen P.J.; Leiros H.-K.S.; Samuelsen, Ørjan. (2019) OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs. mSphere 2019; Volum 4 (2). ISSN 2379-5042.s doi: 10.1128/mSphere.00024-19.*
     

    Teaching

    KJE-3402 - Protein Structure

    F1301- Farmasøytisk kjemi



    CV

    09/2021– 12/2023     Postdoctoral fellow with Prof. Pål Jarle Johnsen at Department of Pharmacy in Enzyme evolution and Structural biology at UiT- The Arctic University of Norway
                                                                                 
    09/2022– 09/2023     Postdoctoral fellow (50%) with Prof. Ole Andreas Økstad at Department of Pharmacy at Oslo University UiO


    08/2017 – 08/2021    Ph.D. candidate in Structural Biology and Evolution with Prof. Hanna-Kirsti Schrøder Leiros at Department of Chemistry UiT- the Arctic University of Norway  


    12/2016 – 10/2017    Lab technician with Prof. Ørjan Samuelsen in the Microbiology Department at the University Hospital Northern Norway


    09/2014 – 11/2016    M.Sc. in Analytical Chemistry at University of Applied Sciences Bonn-Rhein-Sieg (Germany)


    07/2011 – 08/2014    B.Sc. in Pharmaceutical Chemistry at the University of Applied Sciences Cologne (Germany)


    09/2009 – 11/2016    Lab technician in the QC laboratory at the vaccine production unit of MSD Animal Health (Germany)


    08/2006 – 01/2009    Apprentice (chemical lab technician) at Rottendorf GmbH (Germany)