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Antimicrobial Agents and Chemotherapy, December 2005, p. 4876-4883, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.4876-4883.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Channel Formation by CarO, the Carbapenem Resistance-Associated Outer Membrane Protein of Acinetobacter baumannii

UMR 6522 CNRS, PBM, Plate-forme Protéomique IFRMP23, Université de Rouen, F76821 Mont Saint Aignan,¹ UMR 5086 CNRS, Institut de Biologie et Chimie des Protéines, F69367 Lyon,² IFR 1589 Plate-forme Protéomique, F67084 Strasbourg,³ Genoscope and CNRS-UMR8030, Centre National de Séquençage, F91057 Evry Cedex,⁴ EA 2656 GRAM, IFRMP 23, Faculté de Médecine et de Pharmacie, F76000 Rouen, France⁵

Received 29 June 2005/ Returned for modification 26 August 2005/ Accepted 19 September 2005

It has been recently shown that resistance to both imipenem and meropenem in multidrug-resistant clinical strains of Acinetobacter baumannii is associated with the loss of a heat-modifiable 25/29-kDa outer membrane protein, called CarO. This study aimed to investigate the channel-forming properties of CarO. Mass spectrometry analyses of this protein band detected another 25-kDa protein (called Omp25), together with CarO. Both proteins presented similar physicochemical parameters (M_w and pI). We overproduced and purified the two polypeptides as His-tagged recombinant proteins. Circular dichroism analyses demonstrated that the secondary structure of these proteins was mainly a ß-strand conformation with spectra typical of porins. We studied the channel-forming properties of proteins by reconstitution into artificial lipid bilayers. In these conditions, CarO induced ion channels with a conductance value of 110 pS in 1 M KCl, whereas the Omp25 protein did not form any channels, despite its suggested porin function. The pores formed by CarO showed a slight cationic selectivity and no voltage closure. No specific imipenem binding site was found in CarO, and this protein would rather form unspecific monomeric channels.

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