Molecular Characterization of FOX-4, a New AmpC-Type Plasmid-Mediated β-Lactamase from an Escherichia coli Strain Isolated in Spain

A clinical strain of Escherichia coli (Ec GCE) displayed resistance to cefoxitin, cefotetan, cefotaxime, and ceftazidime. Susceptibility was not restored by the addition of clavulanic acid. Two β-lactamases with apparent pIs of 5.4 and 6.4 were identified; the β-lactamase with a pI of 6.4 was transferred by conjugation and associated with a 40-kb plasmid. Analysis of the nucleotide sequence showed a new ampC β-lactamase gene that is closely related to those encoding the FOX-3, FOX-2, and FOX-1 β-lactamases but whose product has four novel amino acid mutations, at positions 11 (M→T), 43 (A→E), 233 (V→A), and 280 (Y→H). This first cephamycinase from Spain was named FOX-4.