Two-component signal transduction in bacteria
Two-component signal transduction systems (TCS) are easily identifiable in genomic databases and are present in more than 95% of the bacterial genomes sequenced to date as well as archaea and eukaryotic organisms such as plants and fungi. Cellular processes regulated by TCS are diverse, ranging from pathogenesis and cell development to metabolism and chemotaxis. Because of the widespread nature of TCS, researchers in many disciplines have reason to experimentally probe the molecular details of how a particular TCS functions in a system of interest.
Two-component signal transduction as potential drug targets in pathogenic bacteria. Curr Opin Microbiol. Feb 3 2010
Gene clusters contributing to processes such as cell growth and pathogenicity are often controlled by two-component signal transduction systems (TCSs). Specific inhibitors against TCS systems work differently from conventional antibiotics, and developing them into new drugs that are effective against various drug-resistant bacteria may be possible. Furthermore, inhibitors of TCSs that control virulence factors may reduce virulence without killing the pathogenic bacteria. Previous TCS inhibitors targeting the kinase domain of the histidine kinase sensor suffered from poor selectivity. Recent TCS inhibitors, however, target the sensory domains of the sensors blocking the quorum sensing system, or target the essential response regulator. These new targets are introduced, together with several specific TCSs that have the potential to serve as effective drug targets.
Summary of useful methods for two-component system research. Curr Opin Microbiol. Feb 3 2010
Since the discovery of protein phosphorylation in bacterial nitrogen assimilation and chemotaxis more than 30 years ago, many biochemical techniques for the analysis of two-component signal transduction systems have been developed. Over time the experimental conditions to follow the flow of phosphate groups from histidine kinases to the cognate response regulators in vitro have been fine tuned. Several approaches were applied to circumvent the instability of the phosphorylated form of response regulator proteins to analyze the structures of their activated forms. Recently, a FRET (fluorescence resonance energy transfer) assay was developed to monitor interactions of chemotaxis proteins in vivo. The availability of bacterial genome sequence databases has facilitated the identification of two-component systems and enabled prediction of interacting kinase-response regulators pairs.
Two component systems in the spatial program of bacteria. Curr Opin Microbiol. Feb 3 2010
Despite being considered a relatively simple form of life, bacteria have revealed a high degree of structural organization, with the spatial destination of their components precisely regulated within the cell. Nevertheless, the primary signals that dictate differential distribution of cellular building blocks and physiological processes remain in most cases largely undisclosed. Signal transduction systems are no exception within this three-dimensional organization and two-component systems (TCS) involved in controlling cell division, differentiation, chemotaxis and virulence show specific and/or dynamic localization, engaging in the spatial program of the bacterial cell.
Tags: Antibiotics, Bacteria, Biology, Microbiology, Science
