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Antimicrobial Agents and Chemotherapy, July 2009, p. 3010-3016, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01164-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Genetic and Biochemical Characterization of the First Extended-Spectrum CARB-Type ß-Lactamase, RTG-4, from Acinetobacter baumannii{triangledown}

Anaïs Potron,1 Laurent Poirel,1 Jacques Croizé,2 Vanessa Chanteperdrix,2 and Patrice Nordmann1*

Service de Bactériologie-Virologie, INSERM U914, Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine et Université Paris-Sud, Le Kremlin-Bicêtre,1 Département de Microbiologie, CHU de Grenoble, Faculté de Médecine, Université Joseph Fourier, Grenoble, France2

Received 29 August 2008/ Returned for modification 20 November 2008/ Accepted 11 April 2009

Acinetobacter baumannii isolate KAR was uncommonly more resistant to cefepime and cefpirome than to ceftazidime and cefotaxime. Cloning and expression of the β-lactamase gene content of this isolate into Escherichia coli TOP10 identified ß-lactamase RTG-4 (or CARB-10), which corresponds to the first reported extended-spectrum CARB-type enzyme. RTG-4 is a plasmid-encoded Ambler class A β-lactamase whose sequence differs by 4 amino acid substitutions from the narrow-spectrum β-lactamase RTG-3. RTG-4 hydrolyzes cefepime and cefpirome and weakly hydrolyzes ceftazidime due to the single Ser-to-Thr substitution at Ambler position 69. RTG-4 is less susceptible to inhibition by tazobactam and sulbactam than RTG-3. Expression of β-lactamase RTG-4 in a wild-type A. baumannii reference strain showed that it conferred resistance to cefepime and cefpirome. The genetic environment of the blaRTG-4 gene was made of a peculiar transposon located on a ca. 50-kb plasmid. ISAba9, located upstream of blaRTG-4, may be responsible for its acquisition by recognizing a secondary right inverted repeat sequence, thus acting by a one-ended transposition process.


* Corresponding author. Mailing address: Service de Bactériologie-Virologie-Hygiène, Hôpital de Bicêtre, 78 rue de Général Leclerc, Le Kremlin-Bicêtre Cedex 94275, France. Phone: 33-1-45-21-36-32. Fax: 33-1-45-21-63-40. E-mail: nordmann.patrice{at}bct.aphp.fr

{triangledown} Published ahead of print on 20 April 2009.


Antimicrobial Agents and Chemotherapy, July 2009, p. 3010-3016, Vol. 53, No. 7
0066-4804/09/$08.00+0     doi:10.1128/AAC.01164-08
Copyright © 2009, American Society for Microbiology. All Rights Reserved.




This article has been cited by other articles:

  • Figueiredo, S., Poirel, L., Papa, A., Koulourida, V., Nordmann, P. (2009). Overexpression of the Naturally Occurring blaOXA-51 Gene in Acinetobacter baumannii Mediated by Novel Insertion Sequence ISAba9. Antimicrob. Agents Chemother. 53: 4045-4047 [Full Text]