Antimicrobial activities of YycG histidine kinase inhibitors against Staphylococcus epidermidis biofilms.
Staphylococcus epidermidis has become a significant pathogen causing infections due to biofilm formation on surfaces of indwelling medical devices. Biofilm-associated bacteria exhibit enhanced resistance to many conventional antibiotics. It is therefore, important to design novel antimicrobial reagents targeting S. epidermidis biofilms. In a static chamber system, the bactericidal effect of two leading compounds active as YycG inhibitors was assessed on biofilm cells by confocal laser scanning microscopy combined with viability staining. In young biofilms (6-h-old), the two compounds killed the majority of the embedded cells at concentrations of 100 microM and 25 microM, respectively. In mature biofilms (24-h-old), one compound was still effectively killing biofilm cells, whereas the other compound mainly killed cells located at the bottom of the biofilm. In contrast, vancomycin was found to stimulate biofilm development at the MBC (8 microg mL(-1)). Even at a high concentration (128 microg mL(-1)), vancomycin exhibited poor killing on cells embedded in biofilms. The two compounds exhibited faster and more effective killing of S. epidermidis planktonic cells than vancomycin at the early stage of exposure (6 h). The data suggest that the new inhibitors can serve as potential agents against S. epidermidis biofilms when added alone or in concert with other antimicrobial agents.
Qin
Zhiqiang
Z
Key laboratory of Medical Molecular Virology of Ministry of education and public health, Institutes of Biomedical Sciences and Institute of Medical Microbiology, Shanghai Medical School of Fudan University Box 228, Shanghai, China.
Lee
Baoleri
B
Yang
Lei
L
Zhang
Jian
J
Yang
Xiaomei
X
Qu
Di
D
Jiang
Hualiang
H
Molin
Soeren
S
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001431:Bacteriological Techniques; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D018613:Microscopy, Confocal; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*; D013212:Staphylococcus epidermidis / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D014640:Vancomycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D047428:Protein Kinase Inhibitors; D014640:Vancomycin; D011494:Protein Kinases; C515949:YycG protein, Staphylococcus epidermidis