PT  - JOURNAL ARTICLE
AU  - Yang, Liang
AU  - Rybtke, Morten Theil
AU  - Jakobsen, Tim Holm
AU  - Hentzer, Morten
AU  - Bjarnsholt, Thomas
AU  - Givskov, Michael
AU  - Tolker-Nielsen, Tim
TI  - Computer-Aided Identification of Recognized Drugs as <em>Pseudomonas aeruginosa</em> Quorum-Sensing Inhibitors
AID  - 10.1128/AAC.01283-08
DP  - 2009 Jun 01
TA  - Antimicrobial Agents and Chemotherapy
PG  - 2432--2443
VI  - 53
IP  - 6
4099  - http://aac.asm.org/content/53/6/2432.short
4100  - http://aac.asm.org/content/53/6/2432.full
SO  - Antimicrob. Agents Chemother.2009 Jun 01; 53
AB  - Attenuation of Pseudomonas aeruginosa virulence by the use of small-molecule quorum-sensing inhibitors (referred to as the antipathogenic drug principle) is likely to play a role in future treatment strategies for chronic infections. In this study, structure-based virtual screening was used in a search for putative quorum-sensing inhibitors from a database comprising approved drugs and natural compounds. The database was built from compounds which showed structural similarities to previously reported quorum-sensing inhibitors, the ligand of the P. aeruginosa quorum-sensing receptor LasR, and a quorum-sensing receptor agonist. Six top-ranking compounds, all recognized drugs, were identified and tested for quorum-sensing-inhibitory activity. Three compounds, salicylic acid, nifuroxazide, and chlorzoxazone, showed significant inhibition of quorum-sensing-regulated gene expression and related phenotypes in a dose-dependent manner. These results suggest that the identified compounds have the potential to be used as antipathogenic drugs. Furthermore, the results indicate that structure-based virtual screening is an efficient tool in the search for novel compounds to combat bacterial infections.