Skip Navigation


JAC Advance Access originally published online on August 27, 2008
Journal of Antimicrobial Chemotherapy 2008 62(5):991-997; doi:10.1093/jac/dkn339
This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Supplementary Data
Right arrow All Versions of this Article:
62/5/991    most recent
dkn339v1
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 (1)
Right arrowRequest Permissions
Right arrow Disclaimer
Google Scholar
Right arrow Articles by Celenza, G.
Right arrow Articles by Perilli, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Celenza, G.
Right arrow Articles by Perilli, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Natural D240G Toho-1 mutant conferring resistance to ceftazidime: biochemical characterization of CTX-M-43

Giuseppe Celenza1, Carla Luzi1, Massimiliano Aschi2, Bernardetta Segatore1, Domenico Setacci1, Cristina Pellegrini1, Chiara Forcella1, Gianfranco Amicosante1 and Mariagrazia Perilli1,*

1 Department of Biomedical Sciences and Technologies, University of L'Aquila, L'Aquila, Italy 2 Department of Chemistry, Chemical Engineering and Materials, University of L'Aquila, L'Aquila, Italy

Received 1 February 2008; returned 29 April 2008; revised 3 July 2008; accepted 29 July 2008

* Corresponding author. Tel: +39-0862-433489; Fax: +39-0862-433433; E-mail: perilli{at}univaq.it

Objectives: The aim of this article is biochemical and kinetic characterization of CTX-M-43, a natural Asp-240->Gly mutant of CTX-M-44 (ex Toho-1), from a clinical isolate of Acinetobacter baumannii isolated in a Bolivian hospital.

Methods: Steady-state kinetic parameters (Km and kcat) were determined for a large pattern of substrates. Analysis of inactivators and transient inactivators was performed to determine the efficiency of acylation (k+2/K) and the deacylation constant (k+3). Molecular modelling of Michaelis complex of ceftazidime, cefotaxime and ceftibuten, obtained from molecular mechanics calculations, was carried out.

Results: CTX-M-43 showed a general increase in affinity towards all cephalosporins tested, with respect to CTX-M-44. Carbapenems acted as inactivators with a good acylation efficiency for meropenem and ertapenem and significant deacylation constant for imipenem. MICs of imipenem obtained at a higher bacterial inoculum of recombinant Escherichia coli were increased.

Conclusions: Kinetic data and molecular modelling of Michaelis complex confirmed that Asp-240->Gly allows a better accommodation of the bulky C7β aminothiazol-oxyimino substituent, resulting in a general increase in the enzyme affinity towards oxyimino cephalosporins. The ascertained potentialities of CTX-M-type enzymes, supported by the kinetic data and the behaviour of the recombinant E. coli at different bacterial inocula towards carbapenems, make a possible evolution of those enzymes towards a carbapenemase activity plausible.

Keywords: Acinetobacter baumannii , antibiotic resistance , CTX-M-type enzymes , class A


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
 Antimicrob. Agents Chemother.Home page
B. Doublet, S. A. Granier, F. Robin, R. Bonnet, L. Fabre, A. Brisabois, A. Cloeckaert, and F.-X. Weill
Novel Plasmid-Encoded Ceftazidime-Hydrolyzing CTX-M-53 Extended-Spectrum {beta}-Lactamase from Salmonella enterica Serotypes Westhampton and Senftenberg
Antimicrob. Agents Chemother., May 1, 2009; 53(5): 1944 - 1951.
[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.