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1.B.63 The Imipenum resistance-associated porin, CarO (CarO) Family

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, a channel-forming protein. Mass spectrometry analyses of this protein band detected another 25-kDa protein (called Omp25; TC# 1.B.1.11.1) with CarO. Both proteins presented similar physicochemical parameters (MW and pI). Siroy et al. (2005) overproduced and purified the two polypeptides as His-tagged recombinant proteins. Circular dichroism analyses demonstrated that the secondary structure of these proteins consist mainly of beta-strands with spectra typical of porins. They studied the channel-forming properties of both proteins by reconstitution into artificial lipid bilayers. CarO induced ion channels with a conductance value of 110 pS in 1 M KCl, but the Omp25 protein did not form channels despite its suggested porin function. The pores formed by CarO showed slight cation selectivity and no voltage closure. No specific imipenem binding site was found in CarO which may form non-specific monomeric channels.

References associated with 1.B.63 family:

AlQumaizi, K.I., S. Kumar, R. Anwer, and S. Mustafa. (2022). Differential Gene Expression of Efflux Pumps and Porins in Clinical Isolates of MDR. Life (Basel) 12:. 35330171
Fonseca, E.L., E. Scheidegger, F.S. Freitas, R. Cipriano, and A.C. Vicente. (2013). Carbapenem-resistant Acinetobacter baumannii from Brazil: role of carO alleles expression and blaOXA-23 gene. BMC Microbiol 13: 245. 24195496
Siroy, A., V. Molle, C. Lemaître-Guillier, D. Vallenet, M. Pestel-Caron, A.J. Cozzone, T. Jouenne, and E. Dé. (2005). Channel formation by CarO, the carbapenem resistance-associated outer membrane protein of Acinetobacter baumannii. Antimicrob. Agents Chemother. 49: 4876-4883. 16304148
Yang, H., L. Huang, P.A. Barnie, Z. Su, Z. Mi, J. Chen, V. Aparna, D. Kumar, and H. Xu. (2015). Characterization and distribution of drug resistance associated β-lactamase, membrane porin and efflux pump genes in MDR A. baumannii isolated from Zhenjiang, China. Int J Clin Exp Med 8: 15393-15402. 26629028
Zahn, M., T. D''Agostino, E. Eren, A. Baslé, M. Ceccarelli, and B. van den Berg. (2015). Small-Molecule Transport by CarO, an Abundant Eight-Stranded β-Barrel Outer Membrane Protein from Acinetobacter baumannii. J. Mol. Biol. 427: 2329-2339. 25846137
Zhu, L.J., X.Y. Chen, and P.F. Hou. (2019). Mutation of CarO participates in drug resistance in imipenem-resistant Acinetobacter baumannii. J Clin Lab Anal 33: e22976. 31318107