Discovery of a Quorum-Sensing Inhibitor of Drug-Resistant Staphylococcal Infections by Structure-Based Virtual Screening

@article{citeulike:2837681, abstract = {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. 10.1124/mol.107.044164}, author = {Kiran, Madanahally D. and Adikesavan, Nallini V. and Cirioni, Oscar and Giacometti, Andrea and Silvestri, Carmela and Scalise, Giorgio and Ghiselli, Roberto and Saba, Vittorio and Orlando, Fiorenza and Shoham, Menachem and Balaban, Naomi }, citeulike-article-id = {2837681}, doi = {http://dx.doi.org/10.1124/mol.107.044164}, journal = {Mol Pharmacol}, keywords = {quorum-sensing}, month = {May}, number = {5}, pages = {1578--1586}, posted-at = {2008-05-27 15:37:46}, priority = {2}, title = {Discovery of a Quorum-Sensing Inhibitor of Drug-Resistant Staphylococcal Infections by Structure-Based Virtual Screening}, url = {http://dx.doi.org/10.1124/mol.107.044164}, volume = {73}, year = {2008} }

TY - JOUR ID - citeulike:2837681 L3 - citeulike-article-id:2837681 N2 - 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. 10.1124/mol.107.044164 IS - 5 JF - Mol Pharmacol EP - 1586 TI - Discovery of a Quorum-Sensing Inhibitor of Drug-Resistant Staphylococcal Infections by Structure-Based Virtual Screening VL - 73 SP - 1578 KW - quorum-sensing AU - Kiran, Madanahally AU - Adikesavan, Nallini AU - Cirioni, Oscar AU - Giacometti, Andrea AU - Silvestri, Carmela AU - Scalise, Giorgio AU - Ghiselli, Roberto AU - Saba, Vittorio AU - Orlando, Fiorenza AU - Shoham, Menachem AU - Balaban, Naomi PY - 2008/05/01/ UR - http://dx.doi.org/10.1124/mol.107.044164 ER -