title: β-Lactamases: A Focus on Current Challenges.
abstract: β-Lactamases, the enzymes that hydrolyze β-lactam antibiotics, remain the greatest threat to the usage of these agents. In this review, the mechanism of hydrolysis is discussed for both those enzymes that use serine at the active site and those that require divalent zinc ions for hydrolysis. The β-lactamases now include >2000 unique, naturally occurring amino acid sequences. Some of the clinically most important of these are the class A penicillinases, the extended-spectrum β-lactamases (ESBLs), the AmpC cephalosporinases, and the carbapenem-hydrolyzing enzymes in both the serine and metalloenzyme groups. Because of the versatility of these enzymes to evolve as new β-lactams are used therapeutically, new approaches to antimicrobial therapy may be required.
authors.affiliation: Department of Medicine, Case Western Reserve University School of Medicine, Louis Stokes Cleveland Department of Veterans Affairs Medical Center, Cleveland, Ohio 44120.|Departments of Pharmacology, Molecular Biology and Microbiology, Biochemistry, and Proteomics and Bioinformatics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44120.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018440:beta-Lactam Resistance; D065093:beta-Lactamase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D001618:beta-Lactamases / Q000145:classification*; D047090:beta-Lactams / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D065093:beta-Lactamase Inhibitors; D047090:beta-Lactams; D001618:beta-Lactamases