An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity
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- 19 September 2008
- journal article
- other
- Published by American Association for the Advancement of Science (AAAS) in Science
- Vol. 321 (5896) , 1673-1675
- https://doi.org/10.1126/science.1159961
Abstract
FtsZ is an essential bacterial guanosine triphosphatase and homolog of mammalian β-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.Keywords
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