Pathogenicity and Histidine Kinases

Publisher Summary

Bacterial pathogenicity can be viewed as the ability of a bacterium to grow and divide within a host. This chapter reviews the role of two-component signal transduction (TCST) systems as regulators of both pathogenicity and growth in gram-negative and gram-positive bacteria. A comprehensive study of the entire TCST complement of both Streptococcus pneumoniae and Staphylococcus aureus and the effect of defined TCST mutations on viability and pathogencity is also presented. It is apparent that TCSTs interact to control both pathogenicity and bacterial cell growth/survival in an unexpectedly complex manner. Nevertheless, the requirement of selected TCSTs for growth either in vivo or in vitro by pathogenic bacteria has raised the possibility that such systems may form attractive antimicrobial drug targets. High throughput screening of compound libraries used to identify inhibitors of the enzymatic components of these systems gave hits that were unattractive for further development because of their chemical properties or that had low activity. As this has been the common experience of similar screens by other pharmaceutical companies, the use of structuralscreens to find routes to more useful types of inhibitors is suggested.