• Evolution of β-lactamase-mediated cefiderocol resistance 

      Frøhlich, Christopher; Sørum, Vidar; Tokuriki, Nobuhiko; Johnsen, Pål Jarle; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2022-07-11)
      Background: Cefiderocol is a novel siderophore β-lactam with improved hydrolytic stability toward β-lactamases, including carbapenemases, achieved by combining structural moieties of two clinically efficient cephalosporins, ceftazidime and cefepime. Consequently, cefiderocol represents a treatment alternative for infections caused by MDR Gram-negatives.<p> <p>Objectives: To study the role of ...
    • Fluorinated captopril analogues inhibit metallo-β-lactamases and facilitate structure determination of NDM-1 binding pose 

      Kondratieva, Alexandra; Palica, Katarzyna; Frøhlich, Christopher; Rolfsnes Hovd, Rebekka; Leiros, Hanna-Kirsti S.; Erdélyi, Máté; Bayer, Annette (Journal article; Tidsskriftartikkel; Peer reviewed, 2024-01-10)
      Bacterial resistance to the majority of clinically used β-lactam antibiotics is a global health threat and, consequently, the driving force for the development of metallo-β-lactamase (MBL) inhibitors. The rapid evolution of new MBLs calls for new strategies and tools for inhibitor development. In this study, we designed and developed a series of trifluoromethylated captopril analogues as probes for ...
    • Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1 

      Frøhlich, Christopher; Sørum, Vidar; Huber, Sandra; Samuelsen, Ørjan; Berglund, Fanny; Kristiansson, Erik; Kotsakis, Stathis D.; Marathe, Nachiket P.; Larsson, Joakim; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-28)
      <i>Background</i> - MBLs form a large and heterogeneous group of bacterial enzymes conferring resistance to β-lactam antibiotics, including carbapenems. A large environmental reservoir of MBLs has been identified, which can act as a source for transfer into human pathogens. Therefore, structural investigation of environmental and clinically rare MBLs can give new insights into structure–activity ...
    • Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1 

      Frøhlich, Christopher; Sørum, Vidar; Huber, Sandra; Samuelsen, Ørjan; Berglund, Fanny; Kristiansson, Erik; Kotsakis, Stathis D.; Marathe, Nachiket; Larsson, DG Joakim; Leiros, Hanna-Kirsti Schrøder (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-28)
      Background: MBLs form a large and heterogeneous group of bacterial enzymes conferring resistance to b-lactam antibiotics, including carbapenems. A large environmental reservoir of MBLs has been identified, which can act as a source for transfer into human pathogens. Therefore, structural investigation of environmental and clinically rare MBLs can give new insights into structure–activity relationships ...
    • Structural studies of triazole inhibitors with promising inhibitor effects against antibiotic resistance metallo-β-lactamases 

      Muhammad, Zeeshan; Skagseth, Susann; Boomgaren, Marc; Akhter, Sundus; Frøhlich, Christopher; Ismael, Aya; Christopeit, Tony; Bayer, Annette; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-06-18)
      Metallo-β-lactamases (MBLs) are an emerging cause of bacterial antibiotic resistance by hydrolysing all classes of β-lactams except monobactams, and the MBLs are not inhibited by clinically available serine-β-lactamase inhibitors. Two of the most commonly encountered MBLs in clinical isolates worldwide – the New Delhi metallo-β-lactamase (NDM-1) and the Verona integron-encoded metallo-β-lactamase ...
    • ZN148 Is a Modular Synthetic Metallo-beta-Lactamase Inhibitor That Reverses Carbapenem Resistance in Gram-Negative Pathogens In Vivo 

      Samuelsen, Ørjan; Åstrand, Ove Alexander Høgmoen; Frøhlich, Christopher; Heikal, Adam; Skagseth, Susann; Carlsen, Trine Josefine Olsen; Leiros, Hanna-Kirsti S.; Bayer, Annette; Schnaars, Christian; Kildahl-andersen, Geir; Lauksund, Silje; Finke, Sarah; Huber, Sandra; Gjøen, Tor; Andresen, Adriana Magalhaes Santos; Økstad, Ole Andreas; Rongved, Pål (Journal article; Tidsskriftartikkel; Peer reviewed, 2020-05-21)
      Carbapenem-resistant Gram-negative pathogens are a critical public health threat and there is an urgent need for new treatments. Carbapenemases (β-lactamases able to inactivate carbapenems) have been identified in both serine β-lactamase (SBL) and metallo-β-lactamase (MBL) families. The recent introduction of SBL carbapenemase inhibitors has provided alternative therapeutic options. Unfortunately, ...