Selection for high-level telithromycin resistance in Staphylococcus aureus yields mutants resulting from an

Daniel R Gentry1, David J Holmes

  • 1Department of Microbiology, ID-CEDD, GlaxoSmithKline, Collegeville, Pennsylvania 19426, USA. dan.r.gentry@gsk.com

Insights

Most Staphylococcus aureus mutants resistant to telithromycin had duplications in rplV. However, four isolates showed insertions in rplV, suggesting a novel gene conversion-like event in ribosomal protein L2 gene mutation.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Genetics

Background:

  • Staphylococcus aureus is a common pathogen.
  • Antibiotic resistance in S. aureus is a growing concern.
  • Telithromycin is a macrolide antibiotic used to treat S. aureus infections.

Purpose of the Study:

  • To investigate the genetic mechanisms of telithromycin resistance in Staphylococcus aureus.
  • To identify novel mutations conferring telithromycin resistance.

Main Methods:

  • Isolation and characterization of telithromycin-resistant Staphylococcus aureus mutants.
  • DNA sequencing to identify mutations in the rplV and rplB genes.

Main Results:

  • Most resistant mutants had duplications in the rplV gene.
  • Four isolates exhibited insertions within rplV, identical to a portion of the rplB gene.
  • These insertions represent a novel mutation mechanism, likely a gene conversion-like event.

Conclusions:

  • A novel gene conversion-like mechanism contributes to telithromycin resistance in Staphylococcus aureus.
  • Understanding these resistance mechanisms is crucial for developing new antimicrobial strategies.

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