• Cryptic β-Lactamase Evolution Is Driven by Low β-Lactam Concentrations 

      Fröhlich, Christopher; Gama, João Alves; Harms, Klaus; Hirvonen, Viivi H. A.; Lund, Bjarte Aarmo; van der Kamp, Marc W.; Johnsen, Pål Jarle; Samuelsen, Ørjan; Leiros, Hanna-Kirsti S. (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-04-28)
      Our current understanding of how low antibiotic concentrations shape the evolution of contemporary β-lactamases is limited. Using the widespread carbapenemase OXA-48, we tested the long-standing hypothesis that selective compartments with low antibiotic concentrations cause standing genetic diversity that could act as a gateway to developing clinical resistance. Here, we subjected <i>Escherichia ...
    • Evolution of β-lactamases and enzyme promiscuity 

      Fröhlich, Christopher; Chen, John Z; Gholipour, Sevan; Erdogan, Ayse N; Tokuriki, Nobuhiko (Journal article; Tidsskriftartikkel; Peer reviewed, 2021-06-08)
      β-Lactamases represent one of the most prevalent resistance mechanisms against β-lactam antibiotics. Beyond their clinical importance, they have also become key models in enzymology and evolutionary biochemistry. A global understanding of their evolution and sequence and functional diversity can therefore aid a wide set of different disciplines. Interestingly, β-lactamases have evolved multiple times ...
    • OXA-48-Mediated Ceftazidime-Avibactam Resistance Is Associated with Evolutionary Trade-Offs 

      Fröhlich, Christopher; Sørum, Vidar; Thomassen, Ane Molden; Johnsen, Pål Jarle; Samuelsen, Ørjan (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-03-27)
      Infections due to carbapenemase-producing Gram-negative pathogens are associated with limited treatment options and consequently lead to increased mortality and morbidity. In response, combinations of existing β-lactams and novel β-lactamase inhibitors, such as ceftazidime-avibactam (CAZ-AVI), have been developed as alternative treatment options. To understand the development of resistance and ...
    • Synthesis and biological evaluation of new dipicolylamine zinc chelators as metallo-β-lactamase inhibitors 

      Prandina, Anthony; Radix, Sylvie; Le Borgne, Marc; Jordheim, Lars Petter; Bousfiha, Zineb; Fröhlich, Christopher; Leiros, Hanna-Kirsti S.; Samuelsen, Ørjan; Frøvold, Espen; Rongved, Pål; Åstrand, Ove Alexander Høgmoen (Journal article; Tidsskriftartikkel; Peer reviewed, 2019-02-02)
      Antibiotics are key drugs in modern healthcare, especially in hospitals, where multiresistant bacteria resides and is a potential threat to human health. In the present work, a new series of adjuvants working synergistically with the carbapenem meropenem, in which a selective zinc-chelating agent was covalently linked to the small bacterial peptide D-Ala-D-Ala, was synthesized and tested against ...