The Redox-Sensing Regulator Rex Contributes to the Virulence and Oxidative Stress Response of Streptococcus suis Serotype 2

Streptococcus suis serotype 2 (SS2) is an important zoonotic pathogen responsible for septicemia and meningitis. The redox-sensing regulator Rex has been reported to play critical roles in the metabolism regulation, oxidative stress response, and virulence of various pathogens. In this study, we identified and characterized a Rex ortholog in the SS2 virulent strain SS2-1 that is involved in bacterial pathogenicity and stress environment susceptibility. Our data show that the Rex-knockout mutant strain Delta rex exhibited impaired growth in medium with hydrogen peroxide or a low pH compared with the wildtype strain SS2-1 and the complementary strain C Delta rex. In addition, Delta rex showed a decreased level of survival in whole blood and in RAW264.7 macrophages. Further analyses revealed that Rex deficiency significantly attenuated bacterial virulence in an animal model. A comparative proteome analysis found that the expression levels of several proteins involved in virulence and oxidative stress were significantly different in Delta rex compared with SS2-1. Electrophoretic mobility shift assays revealed that recombinant Rex specifically bound to the promoters of target genes in a manner that was modulated by NADH and NAD(+). Taken together, our data suggest that Rex plays critical roles in the virulence and oxidative stress response of SS2.