Underlying Mechanism of In vivo and In vitro Activity of C-terminal-amidated Thanatin Against Clinical Isolates of Extended-Spectrum β-lactamase-Producing Escherichia coli
Underlying Mechanism of In vivo and In vitro Activity of C-terminal-amidated Thanatin Against Clinical Isolates of Extended-Spectrum β-lactamase-Producing Escherichia coli
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DOI：
10.1093/infdis/jiq029
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发表时间：
2011-01-15
影响因子：
6.4
通讯作者：
Luo, Xiaoxing
中科院分区：
文献类型：
--
作者：
Hou, Zheng;Lu, Jun;Luo, Xiaoxing
背景。广谱β -内酰胺酶产生大肠杆菌（ESBL-EC）感染已对目前的治疗产生耐药性。因此，本研究旨在探讨c端修饰thanatin （A-thanatin）对ESBL-EC临床分离株体内和体外活性的潜在机制。合成A-thanatin，测定其对ESBL-EC的最小抑菌浓度（MIC）、最小杀菌浓度（MBC）和杀伤曲线。测定了A-thanatin的溶血毒性、稳定性和耐药诱导。用esbl - ec感染小鼠测定A-thanatin的体内活性。采用扫描电镜、透射电镜和荧光显微镜对a -thanatin的作用机理进行了研究。A-thanatin在体外对ESBL-EC非常有效，具有MIC值
Background. Infections with extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-EC) have developed resistance to current therapies. Therefore, the underlying mechanisms of in vivo and in vitro activity of C-terminal-amidated thanatin (A-thanatin) against clinical isolates of ESBL-EC were studied in an attempt to resolve this problem.Methods. A-thanatin was synthesized to determine its minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and kill curve for ESBL-EC. The hemolytic toxicity, stability, and resistance induction of A-thanatin were determined. ESBL-EC-infected mice were used to determine the in vivo activity of A-thanatin. Scanning and transmission electron microscopy and fluorescence microscopy were used to study the underlying mechanism of A-thanatin.Results. A-thanatin is highly effective against ESBL-EC in vitro, with MIC values