title: Epidemiological expansion, structural studies, and clinical challenges of new β-lactamases from gram-negative bacteria.
abstract: β-Lactamase evolution presents to the infectious disease community a major challenge in the treatment of infections caused by multidrug-resistant gram-negative bacteria. Because over 1,000 of these naturally occurring β-lactamases exist, attempts to correlate structure and function have become daunting. Although new enzymes in the extended-spectrum β-lactamase (ESBL) families are frequently identified, the older CTX-M-14 and CTX-M-15 enzymes have become the most prevalent ESBLs in global surveillance. Carbapenemases with either serine-based or zinc-facilitated hydrolysis mechanisms are posing some of the most critical problems. Most geographical regions now report KPC serine carbapenemases and the metallo-β-lactamases VIM, IMP, and NDM-1, even though NDM-1 was only recently identified. The rapid emergence of these newer enzymes, with multiple β-lactamases appearing in a single organism, makes the design of new β-lactamase inactivators or β-lactamase-stable β-lactams all the more difficult. Combination therapy will likely be required to counteract the continuing evolution of these insidious enzymes in multidrug-resistant pathogens.
authors: Biology Department, Indiana University, Bloomington, Indiana 47401, USA. karbush@indiana.edu
authors: Karen
authors: K
authors: Bush
authors: Jed F
authors: JF
authors: Fisher
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024901:Drug Resistance, Multiple, Bacterial; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000737:chemistry / Q000187:drug effects / Q000201:enzymology* / Q000235:genetics; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D006801:Humans; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D065093:beta-Lactamase Inhibitors; D001618:beta-Lactamases