PerR-Regulated Manganese Import Contributes to Oxidative Stress Defense in Streptococcus suis

Streptococcus suis has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Metal homeostasis plays a critical role in the antioxidative capability of bacteria, thus facilitating the escape of pathogenic species from the innate immunity systems of hosts. Here, we revealed that manganese increased the ability of S. suis to resist oxidative stress. RNA sequencing was used to identify potential candidate genes involved in the maintenance of intracellular manganese homeostasis. Four genes, termed troABCD, were identified by NCBI BLASTp analysis. The troA, troB, troC, and troD deletion mutant strains exhibited decreased intracellular manganese content and tolerance to H₂O₂ compared to the wild-type strain. Thus, troABCD were determined to be involved in manganese uptake and played an important role in H₂O₂ tolerance in S. suis. Furthermore, the inactivation of perR increased the survival of H₂O₂-pulsed S. suis 2.18-fold and elevated the intracellular manganese content. H₂O₂-pulsed S. suis and perR deletion mutants upregulated troABCD. This finding suggested that H₂O₂ released the suppression of troABCD by perR. In addition, an electrophoretic mobility shift assay (EMSA) showed that PerR at 500 ng binds to the troABCD promoter, indicating that troABCD were directly regulated by PerR. In conclusion, this study revealed that manganese increases tolerance to H₂O₂ by upregulating the expression of troABCD. Moreover, PerR-regulated Mn import in S. suis and increased the tolerance of S. suis to oxidative stress by regulating troABCD. IMPORTANCE During infection, it is extremely important for bacteria to defend against oxidative stress. While manganese plays an important role in this process, its role is unclear in S. suis. Here, we demonstrated that manganese increased S. suis tolerance to oxidative stress. Four manganese ABC transporter genes, troABCD, were identified. Oxidative stress increased the content of manganese in the cell. Furthermore, PerR increased the tolerance to oxidative stress of S. suis by regulating troABCD. Manganese played an important role in bacterial defense against oxidative stress. These findings provide novel insight into the mechanism by which S. suis resists oxidative stress and approaches to inhibit bacterial infection by limiting manganese intake.