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Antimicrobial Agents and Chemotherapy, April 2008, p. 1264-1268, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.00684-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Genetic and Biochemical Characterization of OXA-63, a New Class D β-Lactamase from Brachyspira pilosicoli BM4442{triangledown}

Djalal Meziane-Cherif,1,{dagger} Thierry Lambert,2 Marine Dupêchez,1 Patrice Courvalin,1 and Marc Galimand1*

Unité des Agents Antibactériens, Institut Pasteur, 75724 Paris Cedex 15,1 Centre d'Etudes Pharmaceutiques, 92296 Châtenay-Malabry, France2

Received 24 May 2007/ Returned for modification 10 August 2007/ Accepted 4 January 2008

Brachyspira pilosicoli BM4442, isolated from the feces of a patient with diarrhea at the Hospital Saint-Michel in Paris, was resistant to oxacillin (MIC > 256 µg/ml) but remained susceptible to cephalosporins and to the combination of amoxicillin and clavulanic acid. Cloning and sequencing of the corresponding resistance determinant revealed a coding sequence of 807 bp encoding a new class D β-lactamase named OXA-63. The blaOXA-63 gene was chromosomally located and not part of a transposon or of an integron. OXA-63 shared 54% identity with FUS-1 (OXA-85), an oxacillinase from Fusobacterium nucleatum subsp. polymorphum, and 25 to 44% identity with other class D β-lactamases (DBLs) and contained all the conserved structural motifs of DBLs. Escherichia coli carrying the blaOXA-63 gene exhibited resistance to benzylpenicillin and amoxicillin but remained susceptible to amoxicillin in combination with clavulanic acid. Mature OXA-63 consisted of a 31.5-kDa polypeptide and appeared to be dimeric. Kinetic analysis revealed that OXA-63 exhibited a narrow substrate profile, hydrolyzing oxacillin, benzylpenicillin, and ampicillin with catalytic efficiencies of 980, 250, and 150 mM–1 s–1, respectively. The enzyme did not apparently interact with oxyimino-cephalosporins, imipenem, or aztreonam. Unlike FUS-1 and other DBLs, OXA-63 was strongly inhibited by clavulanic acid (50% inhibitory concentration [IC50] of 2 µM) and tazobactam (IC50 of 0.16 µM) and exhibited low susceptibility to NaCl (IC50 of >2 M). OXA-63 is the first DBL described for the anaerobic spirochete B. pilosicoli.

* Corresponding author. Mailing address: Unité des Agents Antibactériens, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France. Phone: (33) 1 45 68 83 18. Fax: (33) 1 45 68 83 19. E-mail: galimand{at}pasteur.fr

{triangledown} Published ahead of print on 22 January 2008.

{dagger} Present address: Laboratoire de Biochimie Appliquée, Faculté des Sciences, Université Ferhat Abbas, 19000 Sétif, Algeria.

Antimicrobial Agents and Chemotherapy, April 2008, p. 1264-1268, Vol. 52, No. 4
0066-4804/08/$08.00+0     doi:10.1128/AAC.00684-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Mortimer-Jones, S. M., Phillips, N. D., La, T., Naresh, R., Hampson, D. J. (2008). Penicillin resistance in the intestinal spirochaete Brachyspira pilosicoli associated with OXA-136 and OXA-137, two new variants of the class D {beta}-lactamase OXA-63. J Med Microbiol 57: 1122-1128 [Abstract] [Full Text]  


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