title: Horizontal transfer of the OXA-24 carbapenemase gene via outer membrane vesicles: a new mechanism of dissemination of carbapenem resistance genes in Acinetobacter baumannii.
abstract: The resistance of Acinetobacter baumannii strains to carbapenems is a worrying problem in hospital settings. The main mechanism of carbapenem resistance is the expression of β-lactamases (metalloenzymes or class D enzymes). The mechanisms of the dissemination of these genes among A. baumannii strains are not fully understood. In this study we used two carbapenem-resistant clinical strains of A. baumannii (AbH12O-A2 and AbH12O-CU3) expressing the plasmid-borne bla(OXA-24) gene (plasmids pMMA2 and pMMCU3, respectively) to demonstrate that A. baumannii releases outer membrane vesicles (OMVs) during in vitro growth. The use of hybridization studies enabled us to show that these OMVs harbored the bla(OXA-24) gene. The incubation of these OMVs with the carbapenem-susceptible A. baumannii ATCC 17978 host strain yielded full resistance to carbapenems. The presence of the original plasmids harboring the bla(OXA-24) gene was detected in strain ATCC 17978 after the transformation of OMVs. New OMVs harboring bla(OXA-24) were released by A. baumannii ATCC 17978 after it was transformed with the original OMV-mediated plasmids, indicating the universality of the process. We present the first experimental evidence that clinical isolates of A. baumannii may release OMVs as a mechanism of horizontal gene transfer whereby carbapenem resistance genes are delivered to surrounding A. baumannii bacterial isolates.
authors.affiliation: Servicio de Microbiología, Complejo Hospitalario Universitario La Coruña, 15006 La Coruña, Spain.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rumbo
authors.forename: Esteban
authors.initials: E
authors.lastname: Fernández-Moreira
authors.forename: María
authors.initials: M
authors.lastname: Merino
authors.forename: Margarita
authors.initials: M
authors.lastname: Poza
authors.forename: Jose Antonio
authors.initials: JA
authors.lastname: Mendez
authors.forename: Nelson C
authors.initials: NC
authors.lastname: Soares
authors.forename: Alejandro
authors.initials: A
authors.lastname: Mosquera
authors.forename: Fernando
authors.initials: F
authors.lastname: Chaves
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism; D015780:Carbapenems / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D022761:Gene Transfer, Horizontal / Q000235:genetics / Q000502:physiology*; D046529:Microscopy, Electron, Transmission; D016133:Polymerase Chain Reaction; D022161:Transport Vesicles / Q000378:metabolism*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D001426:Bacterial Proteins; D015780:Carbapenems; D001618:beta-Lactamases; C063912:carbapenemase