An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity Export

@article{citeulike:3349419, abstract = {FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian {beta}-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy. 10.1126/science.1159961}, author = {Haydon, David J. and Stokes, Neil R. and Ure, Rebecca and Galbraith, Greta and Bennett, James M. and Brown, David R. and Baker, Patrick J. and Barynin, Vladimir V. and Rice, David W. and Sedelnikova, Sveta E. and Heal, Jonathan R. and Sheridan, Joseph M. and Aiwale, Sachin T. and Chauhan, Pramod K. and Srivastava, Anil and Taneja, Amit and Collins, Ian and Errington, Jeff and Czaplewski, Lloyd G.}, citeulike-article-id = {3349419}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1159961}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/321/5896/1673}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18801997}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18801997}, day = {19}, doi = {10.1126/science.1159961}, journal = {Science}, keywords = {antibiotics, ftsz}, month = {September}, number = {5896}, pages = {1673--1675}, posted-at = {2008-09-29 11:43:25}, priority = {2}, title = {An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity}, url = {http://dx.doi.org/10.1126/science.1159961}, volume = {321}, year = {2008} }

TY - JOUR ID - citeulike:3349419 L3 - citeulike-article-id:3349419 N2 - FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian {beta}-tubulin that polymerizes and assembles into a ring to initiate cell division. We have created a class of small synthetic antibacterials, exemplified by PC190723, which inhibits FtsZ and prevents cell division. PC190723 has potent and selective in vitro bactericidal activity against staphylococci, including methicillin- and multi-drug-resistant Staphylococcus aureus. The putative inhibitor-binding site of PC190723 was mapped to a region of FtsZ that is analogous to the Taxol-binding site of tubulin. PC190723 was efficacious in an in vivo model of infection, curing mice infected with a lethal dose of S. aureus. The data validate FtsZ as a target for antibacterial intervention and identify PC190723 as suitable for optimization into a new anti-staphylococcal therapy. 10.1126/science.1159961 IS - 5896 JF - Science EP - 1675 TI - An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity VL - 321 SP - 1673 KW - antibiotics KW - ftsz AU - Haydon, David AU - Stokes, Neil AU - Ure, Rebecca AU - Galbraith, Greta AU - Bennett, James AU - Brown, David AU - Baker, Patrick AU - Barynin, Vladimir AU - Rice, David AU - Sedelnikova, Sveta AU - Heal, Jonathan AU - Sheridan, Joseph AU - Aiwale, Sachin AU - Chauhan, Pramod AU - Srivastava, Anil AU - Taneja, Amit AU - Collins, Ian AU - Errington, Jeff AU - Czaplewski, Lloyd PY - 2008/09/19/ UR - http://dx.doi.org/10.1126/science.1159961 ER -