β-Lactamases: A Survey of Protein Diversity
Marion S. Helfand and Robert A. Bonomo
Affiliation: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd. W151 K104, Cleveland, OH 44106, USA
Bacterial resistance to β-lactam antibiotics and β-lactamase inhibitors is an ever increasing problem that threatens the clinical utility of drugs that form the cornerstone of the antibiotic armamentarium. Especially among Gram-negative pathogens, elaboration of structurally and mechanistically novel β-lactamase enzymes is the most important means by which resistance occurs. An appreciation of the tremendous diversity of these drug-modifying enzymes will assist in understanding why so few generally effective inhibitory agents exist for these unique drug targets. This review will give a general background on the reaction mechanisms and classification schemes of the more than 340 β-lactamase enzymes described to date. A discussion will follow highlighting the emerging Class A SHV and TEM-derived extended-spectrum (ESBLs), and inhibitor-resistant enzymes, non-TEM, non- SHV Class A ESBLs, and carbapenemases, Class B metallo-β-lactamases and some of their novel inhibitors, plasmid and chromosomally encoded Class C enzymes, and finally, the OXA-type oxacillinases, ESBLs, and carbapenemases of Class D. The clinical importance of multiple resistance mechanisms in conjunction with the production of β-lactamase enzymes is emphasized.
Keywords: lactamase, lactam, cephalosporinase, penicillinase
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