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Antimicrobial Agents and Chemotherapy, July 2005, p. 2941-2948, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2941-2948.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Identification of a New Allelic Variant of the Acinetobacter baumannii Cephalosporinase, ADC-7 ß-Lactamase: Defining a Unique Family of Class C Enzymes{ddagger}

Kristine M. Hujer,1,{dagger} Nashaat S. Hamza,2,{dagger} Andrea M. Hujer,1 Federico Perez,1 Marion S. Helfand,1 Christopher R. Bethel,1 Jodi M. Thomson,3 Vernon E. Anderson,4 Miriam Barlow,5 Louis B. Rice,1 Fred C. Tenover,6 and Robert A. Bonomo1,3*

Research Service, Louis Stokes Veterans Affairs Medical Center,1 Division of Infectious Diseases, University Hospitals of Cleveland,2 Department of Pharmacology,3 Department of Biochemistry, Case School of Medicine, Cleveland, Ohio,4 Rollins School of Public Health, Emory University, Atlanta, Georgia,5 Division of Healthcare Quality Promotion, Centers for Disease Control and Prevention, Atlanta, Georgia6

Received 17 June 2004/ Returned for modification 19 August 2004/ Accepted 18 March 2005

Acinetobacter spp. are emerging as opportunistic hospital pathogens that demonstrate resistance to many classes of antibiotics. In a metropolitan hospital in Cleveland, a clinical isolate of Acinetobacter baumannii that tested resistant to cefepime and ceftazidime (MIC = 32 µg/ml) was identified. Herein, we sought to determine the molecular basis for the extended-spectrum-cephalosporin resistance. Using analytical isoelectric focusing, a ß-lactamase with a pI of ≥9.2 was detected. PCR amplification with specific A. baumannii cephalosporinase primers yielded a 1,152-bp product which, when sequenced, identified a novel 383-amino-acid class C enzyme. Expressed in Escherichia coli DH10B, this ß-lactamase demonstrated greater resistance against ceftazidime and cefotaxime than cefepime (4.0 µg/ml versus 0.06 µg/ml). The kinetic characteristics of this ß-lactamase were similar to other cephalosporinases found in Acinetobacter spp. In addition, this cephalosporinase was inhibited by meropenem, imipenem, ertapenem, and sulopenem (Ki < 40 µM). The amino acid compositions of this novel enzyme and other class C ß-lactamases thus far described for A. baumannii, Acinetobacter genomic species 3, and Oligella urethralis in Europe and South Africa suggest that this cephalosporinase defines a unique family of class C enzymes. We propose a uniform designation for this family of cephalosporinases (Acinetobacter-derived cephalosporinases [ADC]) found in Acinetobacter spp. and identify this enzyme as ADC-7 ß-lactamase. The coalescence of Acinetobacter ampC ß-lactamases into a single common ancestor and the substantial phylogenetic distance separating them from other ampC genes support the logical value of developing a system of nomenclature for these Acinetobacter cephalosporinase genes.

* Corresponding author. Mailing address: Research Service, Louis Stokes Cleveland Veterans Affairs Medical Center, 10701 East Blvd., Cleveland, OH 44016. Phone: (216) 791-3800, ext. 4399. Fax: (216) 231-3482. E-mail: robert.bonomo{at}med.va.gov.

{ddagger} Supplemental material for this article may be found at http://aac.asm.org/.

{dagger} Contributed equally to this project.

Antimicrobial Agents and Chemotherapy, July 2005, p. 2941-2948, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2941-2948.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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