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Antimicrobial Agents and Chemotherapy, September 2001, p. 2598-2603, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2598-2603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

GES-2, a Class A beta -Lactamase from Pseudomonas aeruginosa with Increased Hydrolysis of Imipenem

Laurent Poirel,1 Gerhard F. Weldhagen,2 Thierry Naas,1 Christophe De Champs,1,3 Michael G. Dove,2 and Patrice Nordmann1,*

Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, 94275 Le Kremlin-Bicêtre,1 and Laboratoire de Bactériologie, Faculté de Médecine, Université d'Auvergne, 63001 Clermont-Ferrand,3 France, and Department of Medical Microbiology, Faculty of Medicine, University of Pretoria, 0001 Pretoria, South Africa2

Received 8 December 2000/Returned for modification 28 March 2001/Accepted 22 June 2001

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, blaGES-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.

* Corresponding author. Mailing address: Service de Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France. Phone: 33-1-45-21-36-32. Fax: 33-1-45-21-63-40. E-mail: nordmann.patrice{at}bct.ap-hop-paris.fr.

Antimicrobial Agents and Chemotherapy, September 2001, p. 2598-2603, Vol. 45, No. 9
0066-4804/01/$04.00+0   DOI: 10.1128/AAC.45.9.2598-2603.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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