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 ...

Metallo--lactamases (MBLs) hydrolyze virtually all -lactam antibiotics, including penicillins, cephalosporins, and carbapenems. The worldwide emergence of antibiotic-resistant bacteria harboring MBLs poses an increasing clinical threat. The MBL German imipenemase-1 (GIM-1) possesses an active site that is narrower and more hydrophobic than the active sites of other MBLs. The GIM-1 active-site ...

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 ...

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 ...

Carbapenemases are the main cause of carbapenem resistance in Gram‐negative bacteria. How β‐lactamases with weak carbapenemase activity, such as the OXA‐10‐type class D β‐lactamases, contribute to anti‐bacterial drug resistance is unclear. OXA‐655 is a T26M and V117L OXA‐10 variant, recently identified from hospital wastewater. Despite exhibiting stronger carbapenemase activity towards ertapenem ...

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 ...