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Antimicrobial Agents and Chemotherapy, March 2006, p. 962-967, Vol. 50, No. 3
0066-4804/06/$08.00+0     doi:10.1128/AAC.50.3.962-967.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Biochemical and Molecular Characterization of Three New Variants of AmpC ß-Lactamases from Morganella morganii

Cátedra de Microbiología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 954, Buenos Aires 1113, Argentina;,¹ Centre d'Ingénierie des Protéines, Université de Liège, Institut de Chimie, B6 (B4000), Sart Tilman, Belgium;,² Centro de Biología Molecular "Severo Ochoa," CSIC-UAM, Campus de Cantoblanco 28049, Madrid, Spain³

Received 10 August 2005/ Returned for modification 4 October 2005/ Accepted 27 November 2005

Morganella morganii produces an inducible, chromosomally encoded AmpC ß-lactamase. We describe in this study three new variants of AmpC within this species with apparent pIs of 6.6 (M19 from M. morganii strain PP19), 7.4 (M29 from M. morganii strain PP29), and 7.8 (M37 from M. morganii strain PP37). After gene sequencing, deduced amino acid sequences displayed one to six substitutions when compared to the available Morganella AmpC sequences. An AmpR-encoding gene was also found upstream of ampC, including the LysR regulators' helix-turn-helix DNA-binding domain and the putative T-N₁₁-A-protected region in the ampR-ampC intercistronic sequence. All three AmpC variants were purified from in vitro-generated derepressed mutants and showed overall similar kinetic parameters. None of the observed amino acid changes, occurring at the surface of the protein, appear to have a major influence in their catalytic properties. Morganella AmpCs exhibit the highest catalytic efficiencies (k_cat/K_m) on classical penicillins, cefoxitin, narrow-spectrum cephalosporins, and cefotaxime. Cefotaxime was more effectively hydrolyzed than other oxyimino-cephalosporins, whereas cefepime was 3 log-fold less efficiently hydrolyzed than other cephalosporins such as cephalothin. Several differences with other AmpC ß-lactamases were found. Ampicillin was more efficiently hydrolyzed than benzylpenicillin. High k_cat/K_m values were observed for oxacillin and piperacillin, which are usually poor substrates for AmpC. A fairly efficient hydrolysis of imipenem was detected as well. Aztreonam, carbenicillin, and tazobactam were effective transient inactivators of these variants.

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