Synergy of Streptogramin Antibiotics Occurs Independently of Their Effects on Translation
Synergy of Streptogramin Antibiotics Occurs Independently of Their Effects on Translation
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DOI：
10.1128/aac.03389-14
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发表时间：
2014-09-01
影响因子：
4.9
通讯作者：
Cate, Jamie H. D.
中科院分区：
文献类型：
--
作者：
Noeske, Jonas;Huang, Jian;Cate, Jamie H. D.
链菌素类抗生素分为A型和B型，两者联合使用可产生协同作用。我们通过X射线晶体学比较了链阳性菌素组合Synercid（A型，达福普汀; B型，奎奴普汀）和NXL 103（A型，氟普汀; B型，利诺普汀）与大肠杆菌70 S核糖体的分子相互作用。我们进一步分析了链阳菌素组分单独和组合的活性。Synercid和NXL 103中的链阳性菌素A和B组分对某些病原菌表现出协同抗菌活性。然而，在转录偶联翻译测定中，仅包括达福普汀（Synercid的链阳性菌素A组分）的组合显示协同作用。值得注意的是，达福普汀中的二乙基氨基乙基磺酰基降低了其活性，但在其从缩肽核心快速水解之前，是转录偶联翻译测定中协同作用的基础。因此，用不可水解基团取代达福普汀中的二乙基氨基乙基磺酰基可能有利于协同作用。在转录偶联翻译试验中，一般链阳性菌素协同作用的缺乏表明链阳性菌素的协同抗菌活性可以独立于链阳性菌素对翻译的影响而发生。
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.