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An inhibitor of FtsZ with potent and selective anti-staphylococcal activity

Lookup NU author(s): Professor Jeff Errington FRSORCiD


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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.

Publication metadata

Author(s): Haydon D, Stokes N, Ure R, Galbraith G, Bennett J, Brown D, Baker P, Barynin V, Rice D, Sedelnikova S, Heal J, Sheridan J, Aiwale S, Chauhan P, Srivastava A, Taneja A, Collins I, Errington J, Czaplewski L

Publication type: Article

Publication status: Published

Journal: Science

Year: 2008

Volume: 321

Issue: 5896

Pages: 1673-1675

ISSN (print): 0036-8075

ISSN (electronic): 1095-9203

Publisher: American Association for the Advancement of Science


DOI: 10.1126/science.1159961


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Funder referenceFunder name
L. Clay and East Hill Management (Boston, MA, USA)
UK Biotechnology and Biological Sciences Research Council
Wellcome Trust under the Seeding Drug Discovery Initiative
UK Department of Trade and Industry