Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis
Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis
复制标题
靶向组氨酸激酶 YycG 的噻唑烷酮衍生物可有效对抗浮游和生物膜相关的表皮葡萄球菌
DOI：
10.1038/aps.2011.166
复制
发表时间：
2012-03-01
影响因子：
8.2
通讯作者：
Qu, Di
中科院分区：
文献类型：
--
作者：
Huang, Ren-zheng;Zheng, Li-kang;Qu, Di
目的：评价新型噻唑二酮类组氨酸激酶抑制剂化合物2的6种衍生物对医疗器械相关生物被膜感染的治疗作用。方法：采用大容量稀释法测定化合物2的最低抑菌浓度，将每管10 0μL的最低抑菌浓度从最低抑菌浓度测定中继代至无药米勒-辛顿琼脂平板。用半定量平板法检测未成熟(6h)生物膜的杀灭作用，用激光共聚焦扫描显微镜(CLSM)观察对成熟(24h)生物膜的杀灭作用。结果：衍生物对表皮葡萄球菌的生长有明显的抑制作用。衍生物H2-10、H2-12、H2-20、H2-29、H2-27、H2-28对S表皮线虫ATCC 35984的MIC值分别为24.3、6.5、6.2、3.3、3.1、1.5μg/m L。这些衍生物的MBC值分别为48.6、52.2、12.4、52.6、12.4和6.2μg/mL。这些衍生物杀死了未成熟(6h)生物膜中的所有细菌，并消除了生物膜的增殖。抗YycG新化合物对成熟(24 H)生物膜细胞具有较强的杀菌活性，而对Vero细胞和人红细胞的细胞毒性和溶血活性较低。结论：新型抗YycG化合物的杀菌和生物膜杀灭活性明显优于母体化合物2。
Aim:To evaluate the efficacies of six derivatives of Compound 2, a novel YycG histidine kinase inhibitor with the thiazolidione core structure in the treatment of medical device-related biofilm infections.Methods:The minimal inhibitory concentration (MIC) of the derivatives was determined using the macrodilution broth method, and the minimal bactericidal concentration (MBC) was obtained via sub-culturing 100 μL from each negative tube from the MIC assay onto drug-free Mueller-Hinton agar plates. Biofilm-killing effect for immature (6 h-old) biofilms was examined using a semiquantitative plate assay, and the effect on mature (24 h-old) biofilms was observed under a confocal laser scanning microscope (CLSM).Results:The derivatives potently suppressed the growth of Staphylococcus epidermidis. The MIC values of the derivatives H2-10, H2-12, H2-20, H2-29, H2-27, and H2-28 on S epidermidis ATCC 35984 were 24.3, 6.5, 6.2, 3.3, 3.1, and 1.5 μg/mL, respectively. The MBC values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 μg/mL, respectively. The derivatives killed all bacteria in immature (6 h-old) biofilms and eliminated the biofilm proliferation. The derivatives also displayed strong bactericidal activities toward cells in mature (24 h-old) biofilms, whereas they showed low cytotoxicity and hemolytic activity toward Vero cells and human erythrocytes.Conclusion:The bactericidal and biofilm-killing activities of the new anti-YycG compounds were significantly better than the parent Compound 2.