Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (3)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Randegger, C. C.
Right arrow Articles by Hächler, H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Randegger, C. C.
Right arrow Articles by Hächler, H.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Journal of Antimicrobial Chemotherapy (2001) 47, 547-554
© 2001 The British Society for Antimicrobial Chemotherapy

Amino acid substitutions causing inhibitor resistance in TEM ß-lactamases compromise the extended-spectrum phenotype in SHV extended-spectrum ß-lactamases

Corinne C. Randegger and Herbert Hächler,*

Institute of Medical Microbiology, University of Zürich, PO Box, CH-8028 Zürich, Switzerland

Three amino acid substitutions, Met-69->Ile, Arg-244->Ser and/or Asn-276->Asp, mediate inhibitor resistance (IR) in TEM ß-lactamases. They were introduced in all possible combinations at homologous positions into either SHV-1 or the respective extended-spectrum ß-lactamases (ESBLs), SHV-2 or SHV-5. Susceptibility testing of the resulting set of seven variants of each parental strain, all in an isogenic background, was performed. The phenotypes of the constructions revealed that most substitutions resulted in reduced resistance to most tested single ß-lactam formulations. This decrease over-compensated for the expected increase in inhibitor resistance, so that most mutants showed no rise in resistance to inhibitor/ß-lactam combinations, although increases of MICs from one- to 43-fold compared with the respective parental strains were also measured. Combination of several IR-determining substitutions impaired both phenotypes in the carrier strains even more. None of the 14 mutants derived from the ESBLs, SHV-2 and SHV-5, showed a clinically relevant combined ESBL–IR phenotype. These findings indicate that the SHV ß-lactamase does not benefit proportionally from simultaneous substitution of residues relevant for the ESBL and the IR phenotype.

* Corresponding author. Tel: +41-1-634-26-48; Fax: +41-1-634-49-06; E-mail: haechler{at}immv.unizh.ch


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Antimicrob ChemotherHome page
F. J. Perez-Llarena, M. Cartelle, S. Mallo, A. Beceiro, A. Perez, R. Villanueva, A. Romero, R. Bonnet, and G. Bou
Structure-function studies of arginine at position 276 in CTX-M {beta}-lactamases
J. Antimicrob. Chemother., April 1, 2008; 61(4): 792 - 797.
[Abstract] [Full Text] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.