Abstract
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 FindingsIn 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/SignificanceSak189 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 BgrR/S (bac gene regulatory system).
Highlights
Streptococcus agalactiae is an important cause of neonatal invasive infections and variety of diseases in human and animals [1,2]
Given the certain similarity in the sequences, functions and relative locations of Sak188/Sak189 and HK06/RR06, and b-antigen and CbpA, we suggested that Sak188/Sak189 two-component regulatory systems (TCSs) affected b-antigen expression and virulent properties of S. agalactiae in the same manner as HK06/RR06 affected CbpA in S. pneumoniae
PCR analysis of the bac gene positive strains revealed that the presence of bac gene correlated with the presence of sensor histidine kinase gene sak188 and DNA-binding response regulator gene sak189
Summary
Streptococcus agalactiae (group B streptococcus) is an important cause of neonatal invasive infections and variety of diseases in human and animals [1,2] This bacterium is able to sense the changing environmental conditions and colonize numerous tissues employing different mechanisms of gene regulation. One mechanism for adaptation to changing environment is transcriptional regulation by two-component regulatory systems (TCSs), a family of systems that are widely distributed among many bacterial genera [3] These regulatory systems comprise two proteins, sensor histidine kinase, HK, and DNA-binding response regulator, RR. Streptococcus agalactiae is able to colonize numerous tissues employing different mechanisms of gene regulation, via two-component regulatory systems These systems sense the environmental stimuli and regulate expression of the genes including virulence genes. In S. agalactiae genome, it was adjacent to the bac gene encoding for b-antigen, an important virulence factor
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