Structural Insights into the Anti-methicillin-resistant Staphylococcus aureus (MRSA) Activity of Ceftobiprole
Structural Insights into the Anti-methicillin-resistant Staphylococcus aureus (MRSA) Activity of Ceftobiprole
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DOI：
10.1074/jbc.m112.355644
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发表时间：
2012-09-14
影响因子：
4.8
通讯作者：
Strynadka, Natalie C. J.
中科院分区：
文献类型：
--
作者：
Lovering, Andrew L.;Gretes, Michael C.;Strynadka, Natalie C. J.
耐甲氧西林金黄色葡萄球菌 (MRSA) 是一种对抗生素具有耐药性的金黄色葡萄球菌菌株，困扰着世界各地的医院和社区。最令人担忧的是它对当前最后一道防线抗生素产生耐药性；迫切需要新的疗法来对抗这种病原体。头孢比普罗是最近开发的最新一代头孢菌素，是第一个通过抑制必需的肽聚糖转肽酶（包括 MRSA 的 β-内酰胺耐药决定簇 PBP2a）而显示出抗 MRSA 活性的药物。在这里，我们展示了头孢比普罗与 PBP2a 结合的复合物的结构。该结构首次揭示了有效的 β-内酰胺耐药性 PBP 相互作用的分子细节，从而使我们对头孢比普罗对抗 MRSA 的功效机制有了新的认识。
Methicillin-resistant Staphylococcus aureus (MRSA) is an antibiotic-resistant strain of S. aureus afflicting hospitals and communities worldwide. Of greatest concern is its development of resistance to current last-line-of-defense antibiotics; new therapeutics are urgently needed to combat this pathogen. Ceftobiprole is a recently developed, latest generation cephalosporin and has been the first to show activity against MRSA by inhibiting essential peptidoglycan transpeptidases, including the beta-lactam resistance determinant PBP2a, from MRSA. Here we present the structure of the complex of ceftobiprole bound to PBP2a. This structure provides the first look at the molecular details of an effective beta-lactam-resistant PBP interaction, leading to new insights into the mechanism of ceftobiprole efficacy against MRSA.