This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Schroeder, W. A.
Right arrow Articles by Jensen, S. E.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Schroeder, W. A.
Right arrow Articles by Jensen, S. E.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, November 2002, p. 3568-3573, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3568-3573.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Resistance to ß-Lactamase Inhibitor Protein Does Not Parallel Resistance to Clavulanic Acid in TEM ß-Lactamase Mutants

William A. Schroeder,{dagger} Troy R. Locke, and Susan E. Jensen*

Department of Biological Sciences, University of Alberta, Edmonton, Alberta T6G 2E9, Canada

Received 20 February 2002/ Returned for modification 22 May 2002/ Accepted 19 July 2002

In order to compare patterns of resistance to inhibition by clavulanic acid with patterns of resistance to inhibition by a ß-lactamase inhibitor protein (BLIP), R164S, R244S, and R164S/R244S mutant forms of TEM ß-lactamase were prepared by site-directed mutagenesis. When kinetic parameters were determined for these mutant and wild-type forms of TEM, the single mutants showed properties that were similar to those in the literature but the double mutant showed properties that were very different. The R164S/R244S double mutant form of TEM retained its resistance to inhibition by clavulanic acid (characteristic of the R244S mutation) but lost all its ability to hydrolyze ceftazidime (characteristic of the R164S mutation). While these characteristics are contrary to those previously reported for an R164S/R244S double mutant, this discrepancy resulted from the use of a defective mutant in the earlier study. Both the single and double mutant forms of TEM remained highly sensitive when tested for inhibition by BLIP, showing only slightly increased resistance compared to that of the wild type; this pattern of resistance is quite different from the pattern of clavulanic acid resistance. The slight increases in resistance to inhibition by BLIP seen in the mutants may have been related to the fact that all of the mutations effected changes in the net charge on the TEM protein that could impede interactions with BLIP.

* Corresponding author. Mailing address: Department of Biological Sciences, University of Alberta, CW-405 Biological Sciences Building, Edmonton, Alberta T6G 2E9, Canada. Phone: (780) 492-0830. Fax: (780) 492-9234. E-mail: susan.jensen{at}ualberta.ca.

{dagger} Present address: Cargill Central Research, Minneapolis, MN 55440-5702.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3568-3573, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3568-3573.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.





Copyright © 2010 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»