ArgR is an essential local transcriptional regulator of the arcABC-operon in Streptococcus suis and crucial for biological fitness in acidic environment

Streptococcus suis is one of the most important pathogens in pigs and can also cause severe infections in humans. Despite its clinical relevance very little is known about the factors contributing to its virulence. Recently, we identified a new putative virulence factor in Streptococcus suis, the arginine deiminase system (ADS), an arginine catabolic enzyme system encoded by the arcABC-operon, which enables Streptococcus suis to survive in acidic environment. In this study, we focused on ArgR, an ADS associated regulator belonging to the ArgR/AhrC arginine repressor family. Using an argR knock-out strain we could show that ArgR is essential for arcABC-operon expression and necessary for the biological fitness of Streptococcus suis. By cDNA expression microarray analyses and quantitative real time RT-PCR we found that the arcABC-operon is the only gene cluster regulated by ArgR, which is in contrast to many other bacteria. Reporter gene analysis with gfp under the control of the arcABC promoter demonstrated that ArgR is able to activate the arcABC promoter. Electrophoretic mobility shift assays with fragments of the arcABC promoter and recombinant ArgR, and chromatin immunoprecipitation with antibodies directed against ArgR revealed that ArgR interacts with the arcABC promoter in vitro and in vivo by binding to a region from -147 to 72 bp upstream of the transcriptional start point. Overall our results show that in Streptococcus suis ArgR is an essential, system specific transcriptional regulator of the ADS directly interacting with the arcABC promoter in vivo