Screening of Virulence-Related Transcriptional Regulators in Streptococcus suis

Streptococcus suis (S.suis) is an important zoonotic pathogen that causes many severe diseases in pigs and humans. Virulence-related transcriptional regulators have been widely reported in pathogenic microorganisms, but only a few have been identified in S.suis. Our aim was to screen virulence-related transcriptional regulators in S.suis. A total of 89 such genes were predicted in the S.suis genome, of which 22 were up-regulated and 18 were down-regulated during S.suis infection in mice. To evaluate the roles of these differentially expressed factors in S.suis virulence, deletion mutants were constructed, and 10 mutants were successfully obtained. Among these genes, the deletion of comR, sitR, or sxvR caused significantly decreased virulence in mice, compared to that with the wild-type strain. Moreover, the survival of ΔcomR, ΔsitR, and ΔsxvR mutant strains in blood was significantly reduced both in vitro and in vivo. Furthermore, their pro-inflammatory abilities were also obviously decreased in vivo. The regulatory mechanisms of comR, sitR, and sxvR were then analyzed by whole transcriptome RNA sequencing (RNA-Seq). Results indicated that the absence of comR induced the down-regulation of 17 virulence factors or virulence-related factors, including genes involved in the synthesis of capsules, oxidative stress tolerance, immune evasion, and cell division. Furthermore, three and two virulence factors or virulence-related factors were down-regulated upon deletion of sitR and sxvR, respectively. Thus, this study reports the discovery of three virulence-associated transcriptional regulatory factors in S.suis. These factors could ultimately be targeted to control infection caused by these bacteria.