Identification and characterization of a novel aac(6')-Iag associated with the blaIMP-1-integron in a multidrug-resistant Pseudomonas aeruginosa

PLoS One. 2013 Aug 12;8(8):e70557. doi: 10.1371/journal.pone.0070557. eCollection 2013.

Abstract

In a continuing study from Dec 2006 to Apr 2008, we characterized nine multi-drug resistant Pseudomonas aeruginosa strains isolated from four patients in a ward at the Hiroshima University Hospital, Japan. Pulsed-field gel electrophoresis of SpeI-digested genomic DNAs from the isolates suggested the clonal expansion of a single strain; however, only one strain, NK0009, was found to produce metallo-β-lactamase. PCR and subsequent sequencing analysis indicated NK0009 possessed a novel class 1 integron, designated as In124, that carries an array of four gene cassettes: a novel aminoglycoside (AG) resistance gene, aac(6')-Iag, blaIMP-1, a truncated form of blaIMP-1, and a truncated form of aac(6')-Iag. The aac(6')-Iag encoded a 167-amino-acid protein that shows 40% identity with AAC(6')-Iz. Recombinant AAC(6')-Iag protein showed aminoglycoside 6'-N-acetyltransferase activity using thin-layer chromatography (TLC) and MS spectrometric analysis. Escherichia coli carrying aac(6')-Iag showed resistance to amikacin, arbekacin, dibekacin, isepamicin, kanamycin, sisomicin, and tobramycin; but not to gentamicin. A conjugation experiment and subsequent Southern hybridization with the gene probes for blaIMP-1 and aac(6')-Ig strongly suggested In124 is on a conjugal plasmid. Transconjugants acquired resistance to gentamicin and were resistant to virtually all AGs, suggesting that the In124 conjugal plasmid also possesses a gene conferring resistance to gentamicin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetyltransferases / genetics*
  • Acetyltransferases / metabolism
  • Aminoglycosides / chemistry
  • Aminoglycosides / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Base Sequence
  • Cross Infection / epidemiology
  • Disease Outbreaks
  • Drug Resistance, Multiple, Bacterial / genetics*
  • Gene Order
  • Humans
  • Integrons*
  • Kinetics
  • Molecular Sequence Data
  • Phylogeny
  • Pseudomonas Infections / epidemiology
  • Pseudomonas aeruginosa / classification
  • Pseudomonas aeruginosa / drug effects*
  • Pseudomonas aeruginosa / genetics*
  • Sequence Alignment
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Acetyltransferases
  • aminoglycoside N(6')-acetyltransferase
  • beta-Lactamases

Associated data

  • GENBANK/AB472901

Grants and funding

This work was supported by Grants-in-Aid for Scientific Research on Priority Areas ‘Applied Genomics’ (No. 17019048 to MS) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.