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Antimicrobial Agents and Chemotherapy, May 1998, p. 1042-1044, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

A237T as a Modulating Mutation in Naturally Occurring Extended-Spectrum TEM-Type beta -Lactamases

Jesús Blázquez,* María-Cristina Negri, María-Isabel Morosini, J. M. Gómez-Gómez, and Fernando Baquero

Servicio de Microbiología, Hospital Ramón y Cajal, Madrid 28034, Spain

Received 25 August 1997/Returned for modification 17 December 1997/Accepted 3 March 1998

A TEM-1 beta -lactamase derivative containing the single amino acid substitution A237T slightly increased (from 24 to 32 µg/ml) the cephalothin MIC for Escherichia coli RYC1000 but did not influence the activities of cefotaxime, ceftazidime, and aztreonam (MICs of 0.03, 0.12, and 0.06 µg/ml, respectively). Despite its apparent neutrality, addition of the A237T mutation to the pair of mutations characterizing TEM-10 (R164S and E240K) had a strong effect on substrate preference. Ceftazidime and aztreonam MICs decreased from 128 and 16 µg/ml to 16 and 2 µg/ml, respectively. In contrast, the cefotaxime MIC increased from 0.5 to 4 µg/ml. The acquisition of apparently neutral or even deleterious mutations results in a very effective mechanism of resistance to different beta -lactams that may be simultaneously or subsequently present in the environment. We propose here that the mutation in position 237 is an example of a modulating mutation and that consideration of this type of mutation may be important for understanding the evolution of beta -lactamases.

* Corresponding author. Mailing address: Servicio de Microbiología, Hospital Ramón y Cajal, Carretera de Colmenar Km 9.100, Madrid 28034, Spain. Phone: (34)-1-336 83 30. Fax: (34)-1-336 88 09 or -336 90 16. E-mail: jesus.blazquez{at}hrc.es.

Antimicrobial Agents and Chemotherapy, May 1998, p. 1042-1044, Vol. 42, No. 5
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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