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Background    Streptococcus agalactiae  is able to colonize numerous tissues employing different mechanisms of gene regulation, particularly via two-component regulatory systems. These systems sense the environmental stimuli and regulate expression of the genes including virulence genes. Recently, the novel two-component regulatory system Sak188/Sak189 was identified. In  S. agalactiae  genome, it was adjacent to the  bac  gene encoding for β-antigen, an important virulence factor.    Methodology/Principal Findings  In this study, the  sak188  and  sak189  genes were inactivated, and the functional role of Sak188/Sak189 two-component system in regulation of the β-antigen expression was investigated. It was demonstrated that both transcription of  bac  gene and expression of encoded β-antigen were controlled by Sak189 response regulator, but not Sak188 histidine kinase. It was also found that the regulation occurred at transcriptional level. Finally, insertional inactivation of  sak189  gene, but not  sak188  gene, significantly affected virulent properties of  S. agalactiae .    Conclusions/Significance  Sak189 response regulator is necessary for activation of  bac  gene transcription. It also controls the virulent properties of  S. agalactiae.  Given that the primary functional role of Sak188/Sak189 two-component systems is a control of  bac  gene transcription, this system can be annotated as  Bgr R/S (  b ac   g ene  r egulatory system).

Inactivation of DNA-Binding Response Regulator Sak189 Abrogates β-Antigen Expression and Affects Virulence of Streptococcus agalactiae