Genetic and Biochemical Characterization of OXA-63, a New Class D β-Lactamase from Brachyspira pilosicoli BM4442
In: Antimicrobial agents and chemotherapy, Jg. 52 (2008), Heft 4, S. 1264-1268
Online
academicJournal
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Zugriff:
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.
Titel: |
Genetic and Biochemical Characterization of OXA-63, a New Class D β-Lactamase from Brachyspira pilosicoli BM4442
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Autor/in / Beteiligte Person: | MEZIANE-CHERIF, Djalal ; LAMBERT, Thierry ; DUPECHEZ, Marine ; COURVALIN, Patrice ; GALIMAND, Marc |
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Zeitschrift: | Antimicrobial agents and chemotherapy, Jg. 52 (2008), Heft 4, S. 1264-1268 |
Veröffentlichung: | Washington, DC: American Society for Microbiology, 2008 |
Medientyp: | academicJournal |
Umfang: | print, 20 ref |
ISSN: | 0066-4804 (print) |
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