Synergy of streptogramin antibiotics occurs independently of their effects on translation

Antimicrob Agents Chemother. 2014 Sep;58(9):5269-79. doi: 10.1128/AAC.03389-14. Epub 2014 Jun 23.


Streptogramin antibiotics are divided into types A and B, which in combination can act synergistically. We compared the molecular interactions of the streptogramin combinations Synercid (type A, dalfopristin; type B, quinupristin) and NXL 103 (type A, flopristin; type B, linopristin) with the Escherichia coli 70S ribosome by X-ray crystallography. We further analyzed the activity of the streptogramin components individually and in combination. The streptogramin A and B components in Synercid and NXL 103 exhibit synergistic antimicrobial activity against certain pathogenic bacteria. However, in transcription-coupled translation assays, only combinations that include dalfopristin, the streptogramin A component of Synercid, show synergy. Notably, the diethylaminoethylsulfonyl group in dalfopristin reduces its activity but is the basis for synergy in transcription-coupled translation assays before its rapid hydrolysis from the depsipeptide core. Replacement of the diethylaminoethylsulfonyl group in dalfopristin by a nonhydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that the synergistic antimicrobial activity of streptogramins can occur independently of the effects of streptogramin on translation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use*
  • Crystallography, X-Ray
  • Drug Combinations
  • Drug Synergism
  • Enterococcus faecalis / drug effects
  • Escherichia coli / drug effects
  • Haemophilus influenzae / drug effects
  • Microbial Sensitivity Tests
  • Protein Biosynthesis / drug effects*
  • Ribosomes / drug effects
  • Ribosomes / ultrastructure
  • Staphylococcus aureus / drug effects
  • Streptococcus pneumoniae / drug effects
  • Streptogramin A / administration & dosage
  • Streptogramin A / pharmacology
  • Streptogramin A / therapeutic use
  • Streptogramin B / administration & dosage
  • Streptogramin B / pharmacology
  • Streptogramin B / therapeutic use
  • Streptogramins / administration & dosage
  • Streptogramins / chemistry
  • Streptogramins / pharmacology
  • Streptogramins / therapeutic use*
  • Virginiamycin / administration & dosage
  • Virginiamycin / pharmacology
  • Virginiamycin / therapeutic use


  • Anti-Bacterial Agents
  • Drug Combinations
  • Streptogramins
  • flopristin, linopristin drug combination
  • Virginiamycin
  • quinupristin-dalfopristin
  • Streptogramin B
  • Streptogramin A