Structural highlights
Publication Abstract from PubMedStreptogramin antibiotics are divided into type A and B streptogramins, 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. 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 non-hydrolyzable group may therefore be beneficial for synergy. The absence of general streptogramin synergy in transcription-coupled translation assays suggests that synergistic antimicrobial activity of streptogramins can occur independently of streptogramin effects on translation. Synergy of streptogramin antibiotics occurs independently of their effects on translation.,Noeske J, Huang J, Olivier NB, Giacobbe RA, Zambrowski M, Cate JH Antimicrob Agents Chemother. 2014 Jun 23. pii: AAC.03389-14. PMID:24957822[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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