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Journal of Bacteriology, December 2005, p. 8196-8200, Vol. 187, No. 23
0021-9193/05/$08.00+0     doi:10.1128/JB.187.23.8196-8200.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

New Class of Competitive Inhibitor of Bacterial Histidine Kinases

Raymond Gilmour,¹ J. Estelle Foster,^1, Qin Sheng,¹ Jonathan R. McClain,¹ Anna Riley,¹ Pei-Ming Sun,¹ Wai-Leung Ng,² Dalai Yan,^1, Thalia I. Nicas,¹ Kenneth Henry,¹ and Malcolm E. Winkler^2*

Eli Lilly and Company, Indianapolis, Indiana 46285,¹ Department of Biology, Indiana University, Bloomington, Indiana 47405²

Received 13 July 2005/ Accepted 8 September 2005

Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a starting compound for a new class of histidine kinase inhibitors with antibacterial activity.

Present address: Protana, Inc., 251 Attwell Dr., Toronto, ON, Canada M9W 7H4.

Present address: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202.

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