An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity
In: Science, Jg. 321 (2008-09-19), S. 1673-1675
Online
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Zugriff:
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-drugâresistant 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.
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An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity
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Autor/in / Beteiligte Person: | Taneja, Amit ; Baker, Patrick J. ; Galbraith, Greta ; Bennett, James M. ; Brown, David ; Ure, Rebecca ; Collins, Ian ; Aiwale, Sachin T. ; Stokes, Neil R. ; Sheridan, Joseph M. ; Srivastava, Anil K. ; Errington, Jeff ; Lloyd George Czaplewski ; Haydon, David J. ; Heal, Jonathan R. ; Chauhan, Pramod K. ; Rice, David W. ; Sedelnikova, Sveta ; Barynin, V.V. |
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Zeitschrift: | Science, Jg. 321 (2008-09-19), S. 1673-1675 |
Veröffentlichung: | American Association for the Advancement of Science (AAAS), 2008 |
Medientyp: | unknown |
ISSN: | 1095-9203 (print) ; 0036-8075 (print) |
DOI: | 10.1126/science.1159961 |
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