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An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity
Open accessAbstract
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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Cites
Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (2001) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(00)00129-0 · Cited by 18,139
How Taxol® stabilises microtubule structure
Amos, L. A., & Löwe, J. (1999) · Chemistry & Biology · doi:10.1016/s1074-5521(99)89002-4 · Cited by 248
Cited by
Systems-level antimicrobial drug and drug synergy discovery
Roemer, T., & Boone, C. (2013) · Nature Chemical Biology · doi:10.1038/nchembio.1205 · Cited by 159
Structure and function of a spectrin-like regulator of bacterial cytokinesis
Cleverley, R. M., Barrett, J. R., Baslé, A., Bui, N. K., Hewitt, L., Solovyova, A., Xu, Z.-Q., Daniel, R. A., Dixon, N. E., Harry, E. J., et al. (2014) · Nature Communications · doi:10.1038/ncomms6421 · Cited by 50
Metadata
- Authors
- Haydon, D. J., Stokes, N. R., Ure, R., Galbraith, G., Bennett, J. M., Brown, D. R., Baker, P. J., Barynin, V. V., Rice, D. W., Sedelnikova, S. E., Heal, J. R., Sheridan, J. M., Aiwale, S. T., Chauhan, P. K., Srivastava, A., Taneja, A., Collins, I., Errington, J., & Czaplewski, L. G.
- Venue
- Science
- Published
- 2008-09-19
- Volume
- 321
- Issue
- 5896
- Pages
- 1673-1675
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1986181072
- Cited by
- 452
- References
- 2
- FWCI
- 17.25
- Type
- journal article
- Language
- en
- Open access
- green
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- Haydon, D. J., Stokes, N. R., Ure, R., Galbraith, G., Bennett, J. M., Brown, D. R., Baker, P. J., Barynin, V. V., Rice, D. W., Sedelnikova, S. E., Heal, J. R., Sheridan, J. M., Aiwale, S. T., Chauhan, P. K., Srivastava, A., Taneja, A., Collins, I., Errington, J., & Czaplewski, L. G. (2008). An Inhibitor of FtsZ with Potent and Selective Anti-Staphylococcal Activity. Science. https://doi.org/10.1126/science.1159961
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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