title: Targeting metallo-β-lactamase enzymes in antibiotic resistance.
abstract: The β-lactam antibiotics are essential for the treatment of a wide range of human bacterial diseases. However, a class of zinc-dependent hydrolases known as the metallo-β-lactamase (MBL) can confer bacteria with extended spectrum β-lactam resistance. To date, there are no clinically approved MBL inhibitors, making these enzymes a serious threat to human health. In this review, a structural approach is taken to outline some of the more promising MBL inhibitors and shed light on how the resistance conferred by this emerging class of enzymes may be circumvented in the future.
authors.affiliation: Department of Biochemistry & Molecular Biology & Center for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Dustin T
authors.initials: DT
authors.lastname: King
authors.forename: Natalie C J
authors.initials: NC
authors.lastname: Strynadka
mesh_terms: D052157:Aptamers, Nucleotide / Q000737:chemistry / Q000494:pharmacology; D001419:Bacteria / Q000201:enzymology; D015780:Carbapenems / Q000737:chemistry / Q000494:pharmacology; D020134:Catalytic Domain; D002511:Cephalosporins / Q000737:chemistry / Q000494:pharmacology; D003503:Cyclobutanes / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D010406:Penicillins / Q000737:chemistry / Q000494:pharmacology; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000494:pharmacology; D018440:beta-Lactam Resistance / Q000187:drug effects; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; D015780:Carbapenems; D002511:Cephalosporins; D003503:Cyclobutanes; D004791:Enzyme Inhibitors; D010406:Penicillins; D013438:Sulfhydryl Compounds; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases