High prevalence of 16S rRNA methyltransferases among carbapenemase-producing Enterobacteriaceae in the UK and Ireland

Int J Antimicrob Agents. 2018 Aug;52(2):278-282. doi: 10.1016/j.ijantimicag.2018.03.016. Epub 2018 Mar 27.

Abstract

The emergence of 16S rRNA methyltransferases (16S RMTases) worldwide is a growing concern due to their ability to confer high-level resistance (minimum inhibitory concentrations (MICs) >256 mg/L) to all clinically relevant aminoglycosides. As the occurrence of 16S RMTases in the United Kingdom has not been investigated to date, we screened 806 Enterobacteriaceae isolates displaying high-level aminoglycoside resistance (amikacin, gentamicin and tobramycin MICs ≥64, ≥32 and ≥32 mg/L, respectively) for 16S RMTases either by analysing whole-genome sequence (WGS) data (which were available for 449 isolates) or by polymerase chain reaction. A total of 94.5% (762/806) pan-aminoglycoside-resistant Enterobacteriaceae were positive for one or more 16S RMTase genes; armA was the most common (340, 44.6%) followed by rmtC (146, 19.2%), rmtF (137, 18.0%), rmtB (87, 11.4%) and various two-gene combinations (52, 6.8%). Most (93.4%; 712/762) 16S RMTase producers also carried acquired carbapenemase genes, with blaNDM the most common (592/712; 83.1%). Additionally, high-risk bacterial clones associated with blaNDM were identified in the subset of isolates with WGS data. These included Escherichia coli sequence types (STs) 405 (21.8%, 19/87), 167 (20.7%, 18/87) 410 (12.6%, 11/87) and K. pneumoniae STs 14 (35.6%, 112/315), 231 (15.6%, 49/315) and 147 (10.5%, 33/315). These accounted for 4.2% (15/358), 5.0% (18/358), 3.1% (11/358), 28.2% (101/358), 3.1% (11/358) and 7.0% (25/358) blaNDM-producing isolates, respectively. This study shows that 16S RMTases occur in the UK and Ireland and carbapenemases are particularly prevalent in 16S RMTase-producing Enterobacteriaceae. This association poses a risk to the treatment of multidrug-resistant Gram-negative infections in the clinical setting.

Keywords: 16S RMTase; Aminoglycoside resistance; Multiplex PCR; bla(NDM).

MeSH terms

  • Aminoglycosides / pharmacology
  • Anti-Bacterial Agents / pharmacology
  • Bacterial Proteins / genetics*
  • Bacterial Proteins / metabolism
  • Drug Resistance, Bacterial
  • Escherichia coli / drug effects
  • Escherichia coli / genetics*
  • Escherichia coli / growth & development
  • Escherichia coli Infections / drug therapy
  • Escherichia coli Infections / epidemiology
  • Escherichia coli Infections / microbiology
  • Gene Expression Regulation, Bacterial*
  • Humans
  • Ireland / epidemiology
  • Klebsiella Infections / drug therapy
  • Klebsiella Infections / epidemiology
  • Klebsiella Infections / microbiology
  • Klebsiella pneumoniae / drug effects
  • Klebsiella pneumoniae / genetics*
  • Klebsiella pneumoniae / growth & development
  • Methyltransferases / genetics*
  • Methyltransferases / metabolism
  • Microbial Sensitivity Tests
  • Plasmids / chemistry
  • Plasmids / metabolism
  • Prevalence
  • RNA, Ribosomal, 16S / genetics*
  • United Kingdom / epidemiology
  • Whole Genome Sequencing
  • beta-Lactamases / genetics*
  • beta-Lactamases / metabolism

Substances

  • Aminoglycosides
  • Anti-Bacterial Agents
  • Bacterial Proteins
  • RNA, Ribosomal, 16S
  • Methyltransferases
  • rRNA (adenosine-O-2'-)methyltransferase
  • beta-Lactamases
  • carbapenemase