title: Contribution of acquired carbapenem-hydrolyzing oxacillinases to carbapenem resistance in Acinetobacter baumannii.
abstract: 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 bla(OXA-23), bla(OXA-40), and bla(OXA-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 bla(OXA-23) and bla(OXA-58) genes were also transformed in A. baumannii CIP 70.10. In addition, the bla(OXA-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 bla(OXA-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 beta-lactams, including carbapenems.
authors.affiliation: Service de Bactériologie-Virologie, Hôpital de Bicêtre, 78 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France. nordmann.patrice@bct.ap-hop-paris.fr
authors.forename: Claire
authors.initials: C
authors.lastname: Héritier
authors.forename: Laurent
authors.initials: L
authors.lastname: Poirel
authors.forename: Thierry
authors.initials: T
authors.lastname: Lambert
authors.forename: Patrice
authors.initials: P
authors.lastname: Nordmann
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D000900:Anti-Bacterial Agents / Q000378:metabolism* / Q000494:pharmacology; D015780:Carbapenems / Q000378:metabolism* / Q000494:pharmacology; D003001:Cloning, Molecular; D004269:DNA, Bacterial / Q000032:analysis; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000592:standards; D010957:Plasmids; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D014170:Transformation, Genetic; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000235:genetics / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D004269:DNA, Bacterial; D001618:beta-Lactamases; C108449:oxacillinase