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dc.contributor.authorFrøhlich, Christopher
dc.contributor.authorSørum, Vidar
dc.contributor.authorHuber, Sandra
dc.contributor.authorSamuelsen, Ørjan
dc.contributor.authorBerglund, Fanny
dc.contributor.authorKristiansson, Erik
dc.contributor.authorKotsakis, Stathis D.
dc.contributor.authorMarathe, Nachiket
dc.contributor.authorLarsson, DG Joakim
dc.contributor.authorLeiros, Hanna-Kirsti Schrøder
dc.date.accessioned2021-11-26T14:34:10Z
dc.date.available2021-11-26T14:34:10Z
dc.date.issued2020-05-28
dc.description.abstractBackground: 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 to explore the role of catalytic and second shell residues, which are under selective pressure.<p> <p>Objectives: To investigate the structure and activity of the environmental subclass B1 MBLs MYO-1, SHD-1 and ECV-1.<p> <p>Methods: The respective genes of these MBLs were cloned into vectors and expressed in Escherichia coli. Purified enzymes were characterized with respect to their catalytic efficiency (kcat/Km). The enzymatic activities and MICs were determined for a panel of different b-lactams, including penicillins, cephalosporins and carbapenems. Thermostability was measured and structures were solved using X-ray crystallography (MYO-1 and ECV-1) or generated by homology modelling (SHD-1).<p> <p>Results: Expression of the environmental MBLs in E. coli resulted in the characteristic MBL profile, not affecting aztreonam susceptibility and decreasing susceptibility to carbapenems, cephalosporins and penicillins. The purified enzymes showed variable catalytic activity in the order of <5% to 70% compared with the clinically widespread NDM-1. The thermostability of ECV-1 and SHD-1 was up to 8C higher than that of MYO-1 and NDM-1. Using solved structures and molecular modelling, we identified differences in their second shell composition, possibly responsible for their relatively low hydrolytic activity.<p> <p>Conclusions: These results show the importance of environmental species acting as reservoirs for MBL-encoding genes.en_US
dc.identifier.citationFrøhlich, Sørum, Huber, Samuelsen, Berglund, Kristiansson, Kotsakis, Marathe, Larsson, Leiros. Structural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1. JAC-Antimicrobial Resistance (JAC-AMR). 2020en_US
dc.identifier.cristinIDFRIDAID 1893090
dc.identifier.doi10.1093/jac/dkaa175
dc.identifier.issn2632-1823
dc.identifier.urihttps://hdl.handle.net/10037/23185
dc.language.isoengen_US
dc.publisherOxford Academicen_US
dc.relation.journalJAC-Antimicrobial Resistance (JAC-AMR)
dc.rights.accessRightsopenAccessen_US
dc.rights.holderCopyright 2020 The Author(s)en_US
dc.subjectVDP::Mathematics and natural science: 400::Chemistry: 440en_US
dc.subjectVDP::Matematikk og Naturvitenskap: 400::Kjemi: 440en_US
dc.titleStructural and biochemical characterization of the environmental MBLs MYO-1, ECV-1 and SHD-1en_US
dc.type.versionpublishedVersionen_US
dc.typeJournal articleen_US
dc.typeTidsskriftartikkelen_US
dc.typePeer revieweden_US


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