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没食子酸表没食子儿茶素酯对耐亚胺培南肺炎克雷伯菌临床分离株的协同抗菌和蛋白质组学效应。

Synergistic anti-bacterial and proteomic effects of epigallocatechin gallate on clinical isolates of imipenem-resistant Klebsiella pneumoniae.

机构信息

Department of Biotechnology, Soonchunhyang University, P.O. Box 97, Asan, Chung-Nam 336-600, Republic of Korea.

出版信息

Phytomedicine. 2011 Aug 15;18(11):941-6. doi: 10.1016/j.phymed.2011.03.012. Epub 2011 May 19.

DOI:10.1016/j.phymed.2011.03.012
PMID:21596543
Abstract

Imipenem-resistant Klebsiella pneumoniae (IRKP) were used to explore the synergistic anti-bacterial and proteomic effects of imipenem alone or in combination with epigallocatechin gallate (EGCg). The minimal inhibitory concentrations (MICs) of EGCG for 12 clinically isolated IRKP strains ranged from 300 to 650 μg/ml. Each of the 12 IRKP strains experienced a 4- to 64-fold reduction in the MIC of imipenem upon co-incubation with 0.25 × MIC level of EGCg. The time-kill method was used on the 12 IRKP clinical isolates to evaluate the bactericidal activities of imipenem alone or with EGCg. Compared to imipenem alone, EGCg with imipenem demonstrated enhanced bactericidal activity. Two-dimensional polyacrylamide gel electrophoresis identified eight down-regulated and four up-regulated proteins in the IRKP strain upon exposure to 1 × MIC of EGCg. Analysis of the outer membrane protein profiles of IRKP cultures treated with EGCg revealed unique changes in outer membrane proteins. In addition, scanning electron microscopic analysis demonstrated the presence of cells with wrinkled surfaces containing perforations and irregular rod-shaped forms after treatment with EGCg or imipenem. These studies demonstrate that EGCg can synergize the bacterial activity of imipenem and differentially stimulate the expression of various proteins in IRKP.

摘要

耐亚胺培南肺炎克雷伯菌(IRKP)用于探索亚胺培南单独或与表没食子儿茶素没食子酸酯(EGCG)联合使用的协同抗菌和蛋白质组学效应。12 株临床分离的 IRKP 菌株的 EGCG 最小抑菌浓度(MIC)范围为 300 至 650μg/ml。当与 0.25×MIC 水平的 EGCg 共孵育时,这 12 株 IRKP 菌株中的每一株对亚胺培南的 MIC 均降低了 4 至 64 倍。时间杀伤法用于评估 12 株 IRKP 临床分离株中亚胺培南单独或与 EGCg 联合使用的杀菌活性。与亚胺培南单独使用相比,EGCG 与亚胺培南联合使用显示出增强的杀菌活性。二维聚丙烯酰胺凝胶电泳鉴定出 1×MIC 的 EGCg 暴露后 IRKP 菌株中 8 种下调和 4 种上调的蛋白质。用 EGCg 处理的 IRKP 培养物的外膜蛋白谱分析显示外膜蛋白存在独特变化。此外,扫描电子显微镜分析表明,在用 EGCg 或亚胺培南处理后,存在表面有皱纹的细胞,其中含有穿孔和不规则杆状形式。这些研究表明,EGCG 可以协同增强亚胺培南的细菌活性,并在 IRKP 中差异刺激各种蛋白质的表达。

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