Genetic and biochemical characterization of FUS-1 (OXA-85), a narrow-spectrum class D β-lactamase from Fusobacterium nucleatum subsp. polymorphum

Christine Voha, Jean Denis Docquier, Gian Maria Rossolini, Thierry Fosse

Research output: Contribution to journalArticlepeer-review

Abstract

Previous studies have reported β-lactamase-mediated penicillin resistance in Fusobacterium nucleatum, but no β-lactamase gene has yet been identified in this species. An F. nucleatum subsp. polymorphum strain resistant to penicillin and amoxicillin was isolated from a human periodontitis sample. DNA cloning and sequencing revealed a 765-bp open reading frame encoding a new class D β-lactamase named FUS-1 (OXA-85). A recombinant Escherichia coli strain carrying the blaFUS-1 gene exhibited resistance to amoxicillin with a moderate decrease in the MICs with clavulanic acid. The bla FUS-1 gene was found in two additional clonally unrelated F. nucleatum subsp. polymorphum isolates. It was located on the chromosome in a peculiar genetic environment where a gene encoding a putative transposase-like protein is found, suggesting a possible acquisition of this class D β-lactamase gene. The FUS-1 enzyme showed the closest ancestral relationship with OXA-63 from Brachyspira pilosicoli (53% identity) and with putative chromosomal β-lactamases of Campylobacter spp. (40 to 42% identity). FUS-1 presents all of the conserved structural motifs of class D β-lactamases. Kinetic analysis revealed that FUS-1 exhibits a narrow substrate profile, efficiently hydrolyzing benzylpenicillin and oxacillin. FUS-1 was poorly inactivated by clavulanate and NaC1. FUS-1 is the first example of a class D β-lactamase produced by a gram-negative, anaerobic, rod-shaped bacterium to be characterized.

Original languageEnglish
Pages (from-to)2673-2679
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume50
Issue number8
DOIs
Publication statusPublished - Aug 2006

ASJC Scopus subject areas

  • Pharmacology (medical)

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