Differential Inhibition of Staphylococcus aureus PBP2 by Glycopeptide Antibiotics

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• 作者：Catherine Leimkuhler ; Lan Chen ; Dianah Barrett ; Gianbattista Panzone ; Binyuan Sun ; Brian Falcone ; Markus Oberth&uuml ; r ; Stefano Donadio ; Suzanne Walker ; and Daniel Kahne
• 刊名：Journal of the American Chemical Society
• 出版年：2005
• 出版时间：March 16, 2005
• 年：2005
• 卷：127
• 期：10
• 页码：3250 - 3251
• 全文大小：53K
• 年卷期：v.127,no.10(March 16, 2005)
• ISSN：1520-5126

文摘

The glycopeptide antibiotics prevent maturation of the bacterial cell wall by binding to the terminal D-alanyl-D-alanine moiety of peptidoglycan precursors, thereby inhibiting the enzymes involved in the final stages of peptidoglycan synthesis. However, there are significant differences in the biological activity of particular glycopeptide derivatives that are not related to their affinity for D-Ala-D-Ala. We compare the ability of vancomycin and a set of clinically relevant glycopeptides to inhibit Staphylococcus aureus PBP2 (penicillin binding protein), the major transglycosylase in a clinically relevant pathogen, S. aureus. We report experiments suggesting that activity differences between glycopeptides against this organism reflect a combination of substrate binding and secondary interactions with key enzymes involved in peptidoglycan synthesis.