Abstract
Two component regulatory systems (TCSs) are found in all prokaryotes except mycoplasmas (Fraser et al., 1995; Himmelreich et al., 1996). They play critical roles in sensing and responding to environmental conditions and in bacterial pathogenesis (Hoch, 2000; Inouye & Dutta, 2003; Stock et al., 2000). TCSs consist of a sensor histidine kinase protein, which is usually bound to the bacterial membrane (Wolanin & Stock, 2003), and a cognate response regulator protein, which often acts as a DNA-binding transcription regulator. Autophosphorylation of the histidine kinase component in response to an environmental signal is followed by phosphoryl transfer to the cognate response regulator, which alters the expression of regulon genes needed to respond to the environmental condition.
Most TCSs are not required for bacteria to grow in the absence of stress in laboratory media (Kobayashi et al., 2001; Oshima et al., 2002). However, there are exceptions to this generalization in certain Gram-negative bacteria [e.g. Caulobacter crescentus (Quon et al., 1996)] and in all Gram-positive bacteria with low G+C content in their DNA. Each of these Gram-positive species, which include many important human pathogens (see Table 1), contains homologues of a single essential TCS, whose histidine kinase and response regulator are designated YycG and YycF, respectively. The gene encoding the YycF response regulator is required for growth of these Gram-positive bacteria under all conditions tested (Echenique & Trombe, 2001; Fabret & Hoch, 1998; Martin et al., 1999; Ng et al., 2003). The YycG histidine kinase is required for growth of most Gram-positive species tested to date (Fabret & Hoch, 1998; Martin et al., 1999) or is conditionally required in Streptococcus pneumoniae depleted for the YycF response regulator (Ng et al., 2003).