Thiazolidione derivatives targeting the histidine kinase YycG are effective against both planktonic and biofilm-associated Staphylococcus epidermidis

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 t...

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Bibliographic Details
Published in:Acta pharmacologica Sinica 2012-03, Vol.33 (3), p.418-425
Main Authors: Huang, Ren-zheng, Zheng, Li-kang, Liu, Hua-yong, Pan, Bin, Hu, Jian, Zhu, Tao, Wang, Wei, Jiang, Dan-bin, Wu, Yang, Wu, You-cong, Han, Shi-qing, Qu, Di
Format: Article
Language:English
Subjects:
Anti-Bacterial Agents - pharmacology
Biofilms - drug effects
Biomedical and Life Sciences
Biomedicine
Histidine Kinase
Immunology
Internal Medicine
Medical Microbiology
MIC值
Original
original-article
Pharmacology/Toxicology
Plankton - drug effects
Protein Kinase Inhibitors - pharmacology
Protein Kinases - metabolism
Staphylococcal Infections - drug therapy
Staphylococcal Infections - metabolism
Staphylococcus epidermidis
Staphylococcus epidermidis - drug effects
Staphylococcus epidermidis - metabolism
Thiazoles - pharmacology
Vaccine
共聚焦激光扫描显微镜
最低杀菌浓度
激酶
生物膜
组氨酸
衍生物
表皮葡萄球菌
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Summary: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 pL 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 pp=,/mL, respectively. The MBC values of these derivatives were 48.6, 52.2, 12.4, 52.6, 12.4, and 6.2 pg/mL, respectively. The derivatives killed all bacteria in immature （6 h-old） biofilms and eliminated the biofllm 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 erythro- cytes. Conclusion： The bactericidal and biofilm-killing activities of the new anti-YycG compounds were significantly better than the parent Compound 2.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2011.166