FIM-1, a new acquired metallo-β-lactamase from a Pseudomonas aeruginosa clinical isolate from Italy

Antimicrob Agents Chemother. 2013 Jan;57(1):410-6. doi: 10.1128/AAC.01953-12. Epub 2012 Oct 31.

Abstract

Acquired metallo-β-lactamases (MBLs) are resistance determinants of increasing clinical importance in Gram-negative bacterial pathogens, which confer a broad-spectrum β-lactam resistance, including carbapenems. Several such enzymes have been described since the 1990s. In the present study, a novel acquired MBL, named FIM-1, was identified and characterized. The bla(FIM-1) gene was cloned from a multidrug-resistant Pseudomonas aeruginosa clinical isolate (FI-14/157) cultured from a patient with a vascular graft infection in Florence, Italy. The isolate belonged in the sequence type 235 epidemic clonal lineage. The FIM-1 enzyme is a member of subclass B1 and, among acquired MBLs, exhibited the highest similarity (ca. 40% amino acid identity) with NDM-type enzymes. In P. aeruginosa FI-14/157, the bla(FIM-1) gene was apparently inserted into the chromosome and associated with ISCR19-like elements that were likely involved in the capture and mobilization of this MBL gene. Transfer experiments of the bla(FIM-1) gene to an Escherichia coli strain or another P. aeruginosa strain by conjugation or electrotransformation were not successful. The FIM-1 protein was produced in E. coli and purified by two chromatography steps. Analysis of the kinetic parameters, carried out with the purified enzyme, revealed that FIM-1 has a broad substrate specificity, with a preference for penicillins (except the 6α-methoxy derivative temocillin) and carbapenems. Aztreonam was not hydrolyzed. Detection of this novel type of acquired MBL in a P. aeruginosa clinical isolate underscores the increasing diversity of such enzymes that can be encountered in the clinical setting.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Anti-Bacterial Agents / metabolism*
  • Anti-Bacterial Agents / pharmacology
  • Aztreonam / pharmacology
  • Carbapenems / metabolism*
  • Carbapenems / pharmacology
  • Chromosomes, Bacterial*
  • Cloning, Molecular
  • Enzyme Assays
  • Escherichia coli / genetics
  • Gene Transfer Techniques
  • Humans
  • Kinetics
  • Microbial Sensitivity Tests
  • Molecular Sequence Data
  • Multilocus Sequence Typing
  • Penicillins / metabolism*
  • Penicillins / pharmacology
  • Phylogeny
  • Pseudomonas Infections / drug therapy*
  • Pseudomonas Infections / microbiology
  • Pseudomonas aeruginosa / classification
  • Pseudomonas aeruginosa / drug effects
  • Pseudomonas aeruginosa / enzymology*
  • Pseudomonas aeruginosa / isolation & purification
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Substrate Specificity
  • beta-Lactamases / chemistry
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism*

Substances

  • Anti-Bacterial Agents
  • Carbapenems
  • Penicillins
  • Recombinant Proteins
  • beta-Lactamases
  • Aztreonam

Associated data

  • GENBANK/JX570731