title: Biochemical-genetic analysis and distribution of FAR-1, a class A beta-lactamase from Nocardia farcinica.
abstract: From genomic DNA of the clinical isolate Nocardia farcinica VIC, a 1. 6-kb Sau3AI fragment was cloned and expressed in Escherichia coli JM109. The recombinant strain expressed a beta-lactamase (pI, 4.6), FAR-1, which conferred high levels of resistance to amoxicillin, piperacillin, ticarcillin, and cephalothin. The hydrolysis constants (kcat, Km, Ki, and 50% inhibitory concentration) confirmed the MIC results and showed that FAR-1 activity is inhibited by clavulanic acid and at a low level by tazobactam and sulbactam. Moreover, FAR-1 beta-lactamase hydrolyzes aztreonam (at a low level) without significant activity against ceftazidime, cefotaxime and imipenem. FAR-1 mature protein of molecular mass ca 32 kDa, has less than 60% amino acid identity with any other class A beta-lactamases, being most closely related to PEN-A from Burkholderia cepacia (52%). A blaFAR-1-like gene was found in all studied N. farcinica strains, underlining the constitutive origin of this gene.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre Cédex, France.
authors.forename: F
authors.initials: F
authors.lastname: Laurent
authors.forename: L
authors.initials: L
authors.lastname: Poirel
authors.forename: T
authors.initials: T
authors.lastname: Naas
authors.forename: E B
authors.initials: EB
authors.lastname: Chaibi
authors.forename: R
authors.initials: R
authors.lastname: Labia
authors.forename: P
authors.initials: P
authors.lastname: Boiron
authors.forename: P
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001483:Base Sequence; D003001:Cloning, Molecular; D008969:Molecular Sequence Data; D009615:Nocardia / Q000201:enzymology*; D001618:beta-Lactamases / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D047090:beta-Lactams
chemical_list: D000900:Anti-Bacterial Agents; D047090:beta-Lactams; D001618:beta-Lactamases