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Novel inhibitors of bacterial cytokinesis identified by a cell-based antibiotic screening assay

Lookup NU author(s): Professor Jeff Errington

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Abstract

The continuous emergence of antibiotic resistance demands that novel classes of antibiotics continue to be developed. The division machinery of bacteria is an attractive target because it comprises seven or more essential proteins that are conserved almost throughout the bacteria but are absent from humans. We describe the development of a cell-based assay for inhibitors of cell division and its use to isolate a new inhibitor of FtsZ protein, a key player in the division machinery. Biochemical, cytological and genetic data are presented which demonstrate that FtsZ is the specific target for the compound. We also describe the effects of more potent analogues of the original hit compound that act on important pathogens, again at the level of cell division. The assay and the compounds have the potential to provide novel antibiotics with no pool of pre-existing resistance. They have provided new insight in to cytokinesis in bacteria and offer important reagents for further studies of the cell division machinery.


Publication metadata

Author(s): Stokes NR, Sievers J, Barker S, Bennett JM, Brown DR, Collins I, Errington VM, Foulger D, Hall M, Halsey R, Johnson H, Rose V, Thomaides HB, Haydon DJ, Czaplewski LG, Errington J

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2005

Volume: 280

Issue: 48

Pages: 39709-39715

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.M506741200

DOI: 10.1074/jbc.M506741200


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