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Antimicrobial Agents and Chemotherapy, November 2008, p. 3898-3904, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00403-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genetic Structure Associated with blaOXA-18, Encoding a Clavulanic Acid-Inhibited Extended-Spectrum Oxacillinase{triangledown}

Thierry Naas,1* Fatemeh Namdari,1 Pierre Bogaerts,2 Te-Din Huang,3 Youri Glupczynski,2,3 and Patrice Nordmann1

Service de Bactériologie-Virologie, INSERM U914: Emerging Resistance to Antibiotics, Hôpital de Bicêtre, Assistance Publique-Hôpitaux de Paris, Faculté de Médecine, Université Paris-Sud, Paris, France,1 Laboratoire de Bactériologie, Cliniques Universitaires Mont-Godinne,2 Laboratoire de Bactériologie, Clinique Universitaire Saint-Luc, Université Catholique de Louvain, Louvain, Belgium3

Received 25 March 2008/ Returned for modification 28 May 2008/ Accepted 18 July 2008

The genetic environment of the blaOXA-18 gene encoding a peculiar clavulanic acid-inhibitable Ambler class D extended-spectrum β-lactamase was determined from the prototype OXA-18-producing Pseudomonas aeruginosa MUS clinical isolate. An 8.2-kb genomic DNA fragment containing blaOXA-18 was cloned from P. aeruginosa MUS. Although most oxacillinases are located in integrons, blaOXA-18 lacked gene cassette-specific features. It was bracketed by two duplicated sequences containing ISCR19, a novel insertion sequence of the ISCR family of mobile elements; {Delta}intI1, a truncated integrase gene; and a truncated {Delta}aac6'-Ib gene cassette. It is likely that ISCR19 was at the origin of the blaOXA-18 gene mobilization by a rolling-circle transposition event followed by homologous recombination. Furthermore, analysis of the cloned genomic DNA fragment revealed the presence of the integron-containing blaOXA-20 gene. Concomitantly, three P. aeruginosa clinical isolates, displaying a synergy image as determined by double-disk diffusion tests on cloxacillin-containing plates, were isolated from three patients hospitalized in different wards over a 9-month period at the Saint-Luc University hospital (Brussels, Belgium). These isolates were positive by PCR for blaOXA-18 and blaOXA-20 genes, genetically related to P. aeruginosa MUS as determined by pulsed-field gel electrophoresis, and carried the same blaOXA-18/blaOXA-20-associated genetic structures. This report characterized the genetic elements likely at the origin of blaOXA-18 gene mobilization in P. aeruginosa and suggests the spread of oxacillin-type extended-spectrum β-lactamases in P. aeruginosa at the Saint-Luc University hospital of Brussels, Belgium.

* Corresponding author. Mailing address: Service de Bactériologie-Virologie, Hôpital de Bicêtre, 78 Rue du Général Leclerc, 94275 Le Kremlin-Bicêtre Cedex, France. Phone: 33 1 45 21 29 86. Fax: 33 1 45 21 63 40. E-mail: thierry.naas{at}bct.aphp.fr

{triangledown} Published ahead of print on 28 July 2008.

Antimicrobial Agents and Chemotherapy, November 2008, p. 3898-3904, Vol. 52, No. 11
0066-4804/08/$08.00+0     doi:10.1128/AAC.00403-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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