title: GES-2, a class A beta-lactamase from Pseudomonas aeruginosa with increased hydrolysis of imipenem.
abstract: Pseudomonas aeruginosa GW-1 was isolated in 2000 in South Africa from blood cultures of a 38-year-old female who developed nosocomial pneumonia. This isolate harbored a self-transferable ca. 100-kb plasmid that conferred an expanded-spectrum cephalosporin resistance profile associated with an intermediate susceptibility to imipenem. A beta-lactamase gene, bla(GES-2), was cloned from whole-cell DNA of P. aeruginosa GW-1 and expressed in Escherichia coli. GES-2, with a pI value of 5.8, hydrolyzed expanded-spectrum cephalosporins, and its substrate profile was extended to include imipenem compared to that of GES-1, identified previously in Klebsiella pneumoniae. GES-2 activity was less inhibited by clavulanic acid, tazobactam and imipenem than GES-1. The GES-2 amino acid sequence differs from that of GES-1 by a glycine-to-asparagine substitution in position 170 located in the omega loop of Ambler class A enzymes. This amino acid change may explain the extension of the substrate profile of the plasmid-encoded beta-lactamase GES-2.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre, France.
authors.forename: L
authors.initials: L
authors.lastname: Poirel
authors.forename: G F
authors.initials: GF
authors.lastname: Weldhagen
authors.forename: T
authors.initials: T
authors.lastname: Naas
authors.forename: C
authors.initials: C
authors.lastname: De Champs
authors.forename: M G
authors.initials: MG
authors.lastname: Dove
authors.forename: P
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D000595:Amino Acid Sequence; D003001:Cloning, Molecular; D006868:Hydrolysis; D015378:Imipenem / Q000378:metabolism*; D007328:Insulin / Q000031:analogs & derivatives; D061268:Insulin Lispro; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011550:Pseudomonas aeruginosa / Q000201:enzymology*; D017386:Sequence Homology, Amino Acid; D013845:Thienamycins / Q000378:metabolism*; D018440:beta-Lactam Resistance / Q000502:physiology; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*; D047090:beta-Lactams / Q000494:pharmacology
chemical_list: D007328:Insulin; D061268:Insulin Lispro; D013845:Thienamycins; D047090:beta-Lactams; D015378:Imipenem; C435769:beta-lactamase GES-2; D001618:beta-Lactamases