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Antimicrobial Agents and Chemotherapy, October 2005, p. 4280-4287, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4280-4287.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Unexpected Enzyme TEM-126: Role of Mutation Asp179Glu

J. Delmas,* F. Robin, F. Bittar, C. Chanal, and R. Bonnet

Faculté de Médecine, Centre Hospitalo-Universitaire, Clermont-Ferrand, France

Received 21 April 2005/ Returned for modification 3 June 2005/ Accepted 12 July 2005

The clinical isolate Escherichia coli CF884 exhibited low-level resistance to ceftazidime (4 µg/ml) by a positive double-disk synergy test and apparent susceptibility to cefuroxime, cefotaxime, cefepime, cefpirome, and aztreonam. The enzyme implicated in this phenotype was a novel 180-kb plasmid-encoded TEM-type extended-spectrum ß-lactamase designated TEM-126 which harbors the mutations Asp179Glu and Met182Thr. TEM-126 exhibited significant hydrolytic activity (kcat, 2 s–1) and a Km value of 82 µM against ceftazidime. Molecular dynamics simulations suggested that the substitution Asp179Glu induces subtle conformational changes to the omega loop which may favor the insertion of ceftazidime in the binding site and the correct positioning of the crucial residue Glu166. Overall, these results highlight the remarkable plasticity of TEM enzymes, which can expand their activity against ceftazidime by the addition of one carbon atom in the side chain of residue 179.

* Corresponding author. Mailing address: Laboratoire de Bactériologie, Faculté de Médecine 28, place H. Dunant, Clermont-Ferrand 63001, France. Phone: (33) 4 73 17 81 50. Fax: (33) 4 73 27 74 94. E-mail: julien.delmas{at}u-clermont1.fr.

Antimicrobial Agents and Chemotherapy, October 2005, p. 4280-4287, Vol. 49, No. 10
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.10.4280-4287.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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