Vertical and horizontal dissemination of an IncC plasmid harbouring rmtB 16S rRNA methylase gene, conferring resistance to plazomicin, among invasive ST258 and ST16 KPC-producing Klebsiella pneumoniae

J Glob Antimicrob Resist. 2021 Mar;24:183-189. doi: 10.1016/j.jgar.2020.12.006. Epub 2020 Dec 26.

Abstract

Objectives: Carbapenem resistance in Klebsiella pneumoniae is a major clinical challenge. Aminoglycosides remain an important asset in the current therapeutic arsenal to treat these infections. We examined aminoglycoside resistance phenotypes and genomics in a collection of 100 invasive KPC-producing K. pneumoniae isolates sequentially collected in a Brazilian tertiary hospital between 2014 and 2016.

Methods: Aminoglycoside susceptibility testing was performed. We used a combined long-read (MinION) and short-read (Illumina) whole-genome sequencing strategy to provide a genomic picture of aminoglycoside resistance genes, with particular emphasis on 16S rRNA methyltransferases and related plasmids.

Results: 68% of the strains were resistant to gentamicin and 42% to amikacin, with 35% resistant to both of these commonly used aminoglycosides. We identified the 16S rRNA methyltransferase gene rmtB in 30% of these isolates: 97% (29/30) belonged to sequence type 258 (ST258) and a single isolate to the emergent ST16 clone. In ST258 and ST16 the rmtB gene was located on large IncC plasmids of 177 kb and 174 kb, respectively, highly similar to a plasmid previously identified in Proteus mirabilis in the same hospital. Moreover, 99% of the isolates remained susceptible to the veterinary-approved drug apramycin, currently under clinical development for human medicine.

Conclusion: Such findings in geographically and temporally related isolates suggest a combination of vertical clonal spread as well as horizontal interspecies and intraspecies plasmid transfer. This broad rmtB dissemination in an endemic setting for KPC-producing clones is worrisome since it provides resistance to most clinically available aminoglycosides, including the novel aminoglycoside-modifying enzyme-resistant plazomicin.

Trial registration: ClinicalTrials.gov NCT04105205.

Keywords: 16S rRNA methyltransferase; Aminoglycosides; Apramycin; KPC-producing Klebsiella pneumoniae; Plazomicin; rmtB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacterial Proteins / genetics
  • Brazil
  • Humans
  • Interleukins
  • Klebsiella pneumoniae* / genetics
  • Methyltransferases
  • Microbial Sensitivity Tests
  • Plasmids / genetics
  • RNA, Ribosomal, 16S / genetics
  • Sisomicin / analogs & derivatives
  • beta-Lactamases* / genetics

Substances

  • Bacterial Proteins
  • Interleukins
  • RNA, Ribosomal, 16S
  • interleukin-24
  • Methyltransferases
  • rRNA (adenosine-O-2'-)methyltransferase
  • beta-Lactamases
  • plazomicin
  • Sisomicin

Associated data

  • ClinicalTrials.gov/NCT04105205