RT Journal Article SR Electronic T1 Discovery of a Quorum-Sensing Inhibitor of Drug-Resistant Staphylococcal Infections by Structure-Based Virtual Screening JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 1578 OP 1586 DO 10.1124/mol.107.044164 VO 73 IS 5 A1 Madanahally D. Kiran A1 Nallini Vijayarangan Adikesavan A1 Oscar Cirioni A1 Andrea Giacometti A1 Carmela Silvestri A1 Giorgio Scalise A1 Roberto Ghiselli A1 Vittorio Saba A1 Fiorenza Orlando A1 Menachem Shoham A1 Naomi Balaban YR 2008 UL http://molpharm.aspetjournals.org/content/73/5/1578.abstract AB Staphylococci are a major health threat because of increasing resistance to antibiotics. An alternative to antibiotic treatment is preventing virulence by inhibition of bacterial cell-to-cell communication using the quorum-sensing inhibitor RNAIII-inhibiting peptide (RIP). In this work, we identified 2′,5-di-O-galloyl-d-hamamelose (hamamelitannin) as a nonpeptide analog of RIP by virtual screening of a RIP-based pharmacophore against a database of commercially available small-molecule compounds. Hamamelitannin is a natural product found in the bark of Hamamelis virginiana (witch hazel), and it has no effect on staphylococcal growth in vitro; but like RIP, it does inhibit the quorum-sensing regulator RNAIII. In a rat graft model, hamamelitannin prevented device-associated infections in vivo, including infections caused by methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis strains. These findings suggest that hamamelitannin may be used as a suppressor to staphylococcal infections.