Biochemical characterization of the interactions of the novel pleuromutilin derivative retapamulin with bacterial ribosomes

被引:73
作者
Yan, Kang [1 ]
Madden, Lenore [1 ]
Choudhry, Anthony E. [1 ]
Voigt, Christine S. [1 ]
Copeland, Robert A. [1 ]
Gontarek, Richard R. [1 ]
机构
[1] GlaxoSmithKline Inc, Dept Enzymol & Mechanist Pharmacol, Collegeville, PA 19426 USA
关键词
D O I
10.1128/AAC.00184-06
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Retapamulin is a semisynthetic pleuromutilin derivative being developed as a topical antibiotic for treating bacterial infections of the skin. It is potent in vitro against susceptible and multidrug-resistant organisms commonly associated with bacterial skin infections. We report detailed mode of action studies demonstrating that retapamulin binds to the bacterial ribosome with high affinity, inhibits ribosomal peptidyl transferase activity, and partially inhibits the binding of the initiator tRNA substrate to the ribosomal P-site. Taken together, these data distinguish the mode of action of retapamulin from that of other classes of antibiotics. This unique mode of action may explain the lack of clinically relevant, target-specific cross-resistance of retapamulin with antibacterials in current use.
引用
收藏
页码:3875 / 3881
页数:7
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