PT  - JOURNAL ARTICLE
AU  - Madanahally D. Kiran
AU  - Nallini Vijayarangan Adikesavan
AU  - Oscar Cirioni
AU  - Andrea Giacometti
AU  - Carmela Silvestri
AU  - Giorgio Scalise
AU  - Roberto Ghiselli
AU  - Vittorio Saba
AU  - Fiorenza Orlando
AU  - Menachem Shoham
AU  - Naomi Balaban
TI  - Discovery of a Quorum-Sensing Inhibitor of Drug-Resistant Staphylococcal Infections by Structure-Based Virtual Screening
AID  - 10.1124/mol.107.044164
DP  - 2008 May 01
TA  - Molecular Pharmacology
PG  - 1578--1586
VI  - 73
IP  - 5
4099  - http://molpharm.aspetjournals.org/content/73/5/1578.short
4100  - http://molpharm.aspetjournals.org/content/73/5/1578.full
SO  - Mol Pharmacol2008 May 01; 73
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.