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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Developing Inhibitors to Selectively Target Two-Component and Phosphorelay Signal Transduction Systems of Pathogenic Microorganisms

Author(s): K. Stephenson and J. A. Hoch

Volume 11, Issue 6, 2004

Page: [765 - 773] Pages: 9

DOI: 10.2174/0929867043455765

Price: $65

Abstract

Two-component signal transduction systems and their expanded variants known as phosphorelays are integral elements of the virulence and antimicrobial resistance responses of a wide range of pathogenic bacteria and fungi and also regulate essential functions. As a consequence, two-component systems and phosphorelays are recognized targets for the development of novel antimicrobial agents and a number of chemically synthesized inhibitors from different chemical classes have been identified by compound library screens. However, in the majority of cases these compounds do not appear to be selective for signal transduction pathways and exert their effect by multiple mechanisms of action. The key to designing molecules to selectively disrupt signal transduction may lie with the conserved features of response regulators and the structural analysis of complexes of signaling proteins.

Keywords: two-component system, phosphorelay, sensor histidine kinase, response regulator, virulence


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