Molecular analysis of linezolid resistance in clinical Enterococcus faecium isolates by polymerase chain reaction and pyrosequencing

Eur J Clin Microbiol Infect Dis. 2011 Jan;30(1):121-5. doi: 10.1007/s10096-010-1046-4. Epub 2010 Sep 3.

Abstract

Resistance to linezolid has been associated with a G2576T mutation in the 23 S rRNA gene. Clinical isolates of linezolid-sensitive and linezolid-resistant vancomycin-resistant Enterococcus faecium of a liver transplant patient have been analysed for the G2576T mutation by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), conventional sequencing and pyrosequencing. A clear association between the number of mutated 23 S rRNA genes and the level of linezolid resistance has been demonstrated. Linezolid susceptibility re-emerged after cessation of linezolid therapy; however, the re-initiation of linezolid therapy resulted in the re-emergence of linezolid-resistant strains. Pyrosequencing rapidly detected the number of mutated alleles and is superior to conventional PCR-RFLP for the detection of heterozygous mutations.

MeSH terms

  • Acetamides / pharmacology*
  • Anti-Bacterial Agents / pharmacology*
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / genetics*
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / genetics*
  • Drug Resistance, Bacterial*
  • Enterococcus faecium / drug effects*
  • Enterococcus faecium / genetics
  • Humans
  • Linezolid
  • Oxazolidinones / pharmacology*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • RNA, Ribosomal, 23S / genetics
  • Sequence Analysis, DNA

Substances

  • Acetamides
  • Anti-Bacterial Agents
  • DNA, Bacterial
  • DNA, Ribosomal
  • Oxazolidinones
  • RNA, Ribosomal, 23S
  • Linezolid