1. Synergy of Streptogramin Antibiotics Occurs Independently of Their Effects on Translation
- Author
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Noeske, Jonas, Huang, Jian, Olivier, Nelson B, Giacobbe, Robert A, Zambrowski, Mark, and Cate, Jamie HD
- Subjects
Infectious Diseases ,Infection ,Anti-Bacterial Agents ,Crystallography ,X-Ray ,Drug Combinations ,Drug Synergism ,Enterococcus faecalis ,Escherichia coli ,Haemophilus influenzae ,Microbial Sensitivity Tests ,Protein Biosynthesis ,Ribosomes ,Staphylococcus aureus ,Streptococcus pneumoniae ,Streptogramin A ,Streptogramin B ,Streptogramins ,Virginiamycin ,Microbiology ,Medical Microbiology ,Pharmacology and Pharmaceutical Sciences - Abstract
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. more...
- Published
- 2014