Genetic characterization of Vga ABC proteins conferring reduced susceptibility to pleuromutilins in Staphylococcus

Daniel R Gentry1, Lynn McCloskey, Michael N Gwynn

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

Insights

Six Staphylococcus aureus isolates showed reduced susceptibility to the antibiotic retapamulin. This resistance was linked to specific ABC proteins, VgaAv and VgaA, impacting pleuromutilin effectiveness.

Area of Science:

  • Microbiology
  • Molecular Biology
  • Antimicrobial Resistance

Background:

  • Staphylococcus aureus is a significant human pathogen.
  • Pleuromutilins are a class of antibiotics used to treat bacterial infections.
  • Monitoring antibiotic susceptibility is crucial for effective treatment.

Purpose of the Study:

  • To investigate the prevalence of reduced susceptibility to retapamulin in recent clinical isolates of Staphylococcus aureus.
  • To identify the genetic mechanisms responsible for this reduced susceptibility.

Main Methods:

  • Minimum Inhibitory Concentration (MIC) testing was performed on 5,676 clinical isolates of Staphylococcus aureus.
  • Isolates exhibiting reduced susceptibility were further analyzed to identify resistance genes.

Main Results:

  • Six out of 5,676 S. aureus isolates displayed Minimum Inhibitory Concentrations (MICs) of >= 2 microg/ml for retapamulin.
  • The ATP-binding cassette (ABC) proteins, VgaAv and VgaA, were identified as the cause of reduced susceptibility to pleuromutilins in these isolates.

Conclusions:

  • The ABC proteins VgaAv and VgaA confer reduced susceptibility to pleuromutilins in Staphylococcus aureus.
  • These findings highlight the importance of monitoring for resistance mechanisms to ensure the continued efficacy of retapamulin.

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