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

Abstract

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.

• Authors: Ren-zheng Huang, Li-kang Zheng, Hua-yong Liu, Bin Pan, Jian Hu, Tao Zhu, Wei Wang, Dan-bin Jiang, Yang Wu, You-cong Wu, Shi-qing Han, Di Qu
• Journal: Acta pharmacologica Sinica (Acta Pharmacol Sin) Vol. 33 Issue 3 Pg. 418-25 (Mar 2012) ISSN: 1745-7254 [Electronic] United States
• PMID: 22231397 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Bacterial Agents
• Protein Kinase Inhibitors
• Thiazoles
• Protein Kinases
• Histidine Kinase
• YycG protein, Staphylococcus epidermidis

Topics

• Anti-Bacterial Agents (pharmacology)
• Biofilms (drug effects)
• Histidine Kinase
• Plankton (drug effects)
• Protein Kinase Inhibitors (pharmacology)
• Protein Kinases (metabolism)
• Staphylococcal Infections (drug therapy, metabolism)
• Staphylococcus epidermidis (drug effects, metabolism)
• Thiazoles (pharmacology)