ABSTRACTThe increasing number of carbapenem-resistantAcinetobacter baumanniiisolates 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 thePseudomonas aeruginosaOprD porin. Suspected to be the preferred pathway of carbapenems inA. baumannii, theoprDhomologue 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 theP. aeruginosaOprQ 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 Fe3+and Mg2+, respectively, but not by imipenem and meropenem or basic amino acids. TheA. baumanniiOprD 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.
Structure–function relationships of CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii
