Two-component signal transduction systems in Clostridia

To survive and proliferate in constantly changing surroundings, bacteria have evolved regulatory systems that enable them to monitor and adapt to a diverse range of environmental conditions [1,2]. The most common adaptive response involves twocomponent signal transduction systems. The number of these regulatory systems identified in recent years has increased dramatically; they have been detected in Grampositive and Gram-negative bacteria [2], as well as in some eukaryotes [3,4]. These regulatory networks generally consist of a membrane-associated sensor histidine kinase and its cognate cytoplasmic response regulator, which communicate by a His-Asp phosphorelay that usually culminates in the modulation of gene expression [5-7]. This regulatory cascade is activated upon the detection of the appropriate stimulus by the sensor histidine kinase. This event induces the protein to autophosphorylate, whereby the γ-phosphoryl group in ATP is transferred to a conserved His residue located in the cytoplasmic C-terminal domain. The N-terminal regulatory domain of the cognate response regulator then catalyzes the transfer of the phosphoryl group from the His residue to a conserved Asp residue, which activates the response regulator so it is able to bind to its target DNA and, subsequently, regulate gene expression [1,6,8].