Journal article
Computer-aided identification of recognized drugs as Pseudomonas aeruginosa quorum-sensing inhibitors
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.
Language: | English |
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Publisher: | American Society for Microbiology (ASM) |
Year: | 2009 |
Pages: | 2432-2443 |
ISSN: | 10986596 , 00664804 and 10706283 |
Types: | Journal article |
DOI: | 10.1128/AAC.01283-08 |
ORCIDs: | Rybtke, Morten Theil , 0000-0002-1671-2155 , 0000-0002-8003-7414 , 0000-0001-5004-8609 and 0000-0002-9751-474X |
ANTIBIOTIC-RESISTANCE AUTOINDUCER BACTERIAL BIOFILMS DNA RELEASE INFECTIONS INVOLVEMENT LACTONE MOLECULAR DOCKING POLYMORPHONUCLEAR LEUKOCYTES VIRULENCE FACTORS
Anti-Bacterial Agents Bacterial Proteins Biofilms Chlorzoxazone Computer-Aided Design Dose-Response Relationship, Drug Hydroxybenzoates LasR protein, Pseudomonas aeruginosa Nitrofurans Pseudomonas aeruginosa Quorum Sensing Salicylic Acid Trans-Activators Virulence Factors nifuroxazide