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Antimicrobial Agents and Chemotherapy, August 2005, p. 3198-3202, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3198-3202.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Contribution of Acquired Carbapenem-Hydrolyzing Oxacillinases to Carbapenem Resistance in Acinetobacter baumannii

Claire Héritier,1 Laurent Poirel,1 Thierry Lambert,2 and Patrice Nordmann1*

Service de Bactériologie-Virologie, Hôpital de Bicêtre, Assistance Publique/Hôpitaux de Paris, Faculté de Médecine Paris-Sud, Université Paris XI, 94275 Le Kremlin-Bicêtre,1 Centre d'Etudes Pharmaceutiques, Châtenay-Malabry, France2

Received 2 February 2005/ Returned for modification 21 March 2005/ Accepted 30 May 2005

Carbapenem-hydrolyzing oxacillinases are reported increasingly in Acinetobacter baumannii. Since they hydrolyze carbapenems at low levels, the roles of carbapenem-hydrolyzing oxacillinases OXA-23, OXA-40, and OXA-58 in A. baumannii were determined. The blaOXA-23, blaOXA-40, and blaOXA-58 genes were inserted in broad-host-range plasmid pAT801 and transformed in Escherichia coli DH10B and in A. baumannii CIP 70.10 and its point mutant derivative A. baumannii BM4547, which overexpresses the efflux pump AdeABC. Natural plasmids harboring the blaOXA-23 and blaOXA-58 genes were also transformed in A. baumannii CIP 70.10. In addition, the blaOXA-40 gene was inactivated at its chromosome location in A. baumannii CLA-1. Intermediate levels of resistance or reduced susceptibilities to carbapenems were observed for A. baumannii transformants expressing OXA-23, OXA-40, and OXA-58. The inactivation of blaOXA-40 in A. baumannii CLA-1 yielded reduced susceptibilities to carbapenems. Carbapenem-hydrolyzing oxacillinases OXA-23, OXA-40, and to a lesser extent OXA-58 play a role in carbapenem resistance in A. baumannii, and overexpression of efflux pump AdeABC may also contribute to higher levels of resistance to ß-lactams, including carbapenems.

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

Antimicrobial Agents and Chemotherapy, August 2005, p. 3198-3202, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3198-3202.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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