title: Extended-spectrum AmpC cephalosporinase in Acinetobacter baumannii: ADC-56 confers resistance to cefepime.
abstract: ADC-56, a novel extended-spectrum AmpC (ESAC) β-lactamase, was identified in an Acinetobacter baumannii clinical isolate. ADC-56 possessed an R148Q change compared with its putative progenitor, ADC-30, which enabled it to hydrolyze cefepime. Molecular modeling suggested that R148 interacted with Q267, E272, and I291 through a hydrogen bond network which constrained the H-10 helix. This permitted cefepime to undergo conformational changes in the active site, with the carboxyl interacting with R340, likely allowing for better binding and turnover.
authors.affiliation: Division of Infectious Diseases, University of Pittsburgh School of Medicine, Scaife Hall S829, 3550 Terrace Street, Pittsburgh, PA 15261, USA.
authors.forename: Guo-Bao
authors.initials: GB
authors.lastname: Tian
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Adams-Haduch
authors.forename: Magdalena
authors.initials: M
authors.lastname: Taracila
authors.forename: Robert A
authors.initials: RA
authors.lastname: Bonomo
authors.forename: Hong-Ning
authors.initials: HN
authors.lastname: Wang
authors.forename: Yohei
authors.initials: Y
authors.lastname: Doi
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000235:genetics*; D000077723:Cefepime; D018550:Cephalosporin Resistance / Q000235:genetics; D002510:Cephalosporinase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002511:Cephalosporins / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial; D005798:Genes, Bacterial; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D000077723:Cefepime; D002510:Cephalosporinase; C048795:AmpC beta-lactamases; D001618:beta-Lactamases