title: Deciphering the function of the outer membrane protein OprD homologue of Acinetobacter baumannii.
abstract: The increasing number of carbapenem-resistant Acinetobacter baumannii isolates is a major cause for concern which restricts therapeutic options to treat severe infections caused by this emerging pathogen. To identify the molecular mechanisms involved in carbapenem resistance, we studied the contribution of an outer membrane protein homologue of the Pseudomonas aeruginosa OprD porin. Suspected to be the preferred pathway of carbapenems in A. baumannii, the oprD homologue gene was inactivated in strain ATCC 17978. Comparison of wild-type and mutant strains did not confirm the expected increased resistance to any antibiotic tested. OprD homologue sequence analysis revealed that this protein actually belongs to an OprD subgroup but is closer to the P. aeruginosa OprQ protein, with which it could share some functions, e.g., allowing bacterial survival under low-iron or -magnesium growth conditions or under poor oxygenation. We thus overexpressed and purified a recombinant OprD homologue protein to further examine its functional properties. As a specific channel, this porin presented rather low single-channel conductance, i.e., 28 pS in 1 M KCl, and was partially closed by micro- and millimolar concentrations of Fe(3+) and Mg(2+), respectively, but not by imipenem and meropenem or basic amino acids. The A. baumannii OprD homologue is likely not involved in the carbapenem resistance mechanism, but as an OprQ-like protein, it could contribute to the adaptation of this bacterium to magnesium- and/or iron-depleted environments.
authors.affiliation: University of Rouen, Laboratoire Polymères Biopolymères Surfaces, UMR 6270 and FR 3038 CNRS, IRIB, Mont Saint Aignan, France.
authors.forename: Manuella
authors.initials: M
authors.lastname: Catel-Ferreira
authors.forename: Rony
authors.initials: R
authors.lastname: Nehmé
authors.forename: Virginie
authors.initials: V
authors.lastname: Molle
authors.forename: Jesús
authors.initials: J
authors.lastname: Aranda
authors.forename: Emeline
authors.initials: E
authors.lastname: Bouffartigues
authors.forename: Sylvie
authors.initials: S
authors.lastname: Chevalier
authors.forename: Germán
authors.initials: G
authors.lastname: Bou
authors.forename: Thierry
authors.initials: T
authors.lastname: Jouenne
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Dé
mesh_terms: D040981:Acinetobacter baumannii / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001425:Bacterial Outer Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D001761:Bleomycin / Q000494:pharmacology; D007612:Kanamycin / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000900:Anti-Bacterial Agents; D001425:Bacterial Outer Membrane Proteins; D001761:Bleomycin; C105427:Zeocin; D007612:Kanamycin