Streptococcus suis Dpr provides protection from hydrogen peroxide in an iron rich environment

Introduction: Streptococcus suis (S. suis) is a common porcine pathogen with zoonotic potential. It can cause meningitis, arthritis, septicemia and in humans also the streptococcal toxic shock-like syndrome. S. suis expresses a Dps-like peroxide resistance protein, designated Dpr. The protein prevents production of reactive oxygen species (ROS) by the Fenton-reaction (H₂O₂ + Fe²⁺ → ^.OH + OH^- + Fe³⁺), as it is capable of binding iron and oxidizing Fe²⁺ to Fe³⁺. So far, the structure and the mechanism of iron incorporation by Dpr have been studied at atomic resolution, but its relevance in the pathogenesis of S. suis infection remains to be elucidated.

In this study we aim to understand the role of Dpr in immune evasion as a putative virulence factor protecting against oxidative stress during bacteremia and meningitis.

Methods: We used a formerly created Dpr-deficient mutant (Pulliainen et al. 2003) to investigate its role in different biological settings: survival of S. suis in porcine blood, growth in porcine serum or cerebrospinal fluid (CSF) at increasing H₂O₂ concentrations and sensitivity to H₂O₂ under hemolytic conditions caused by S. suis-produced toxin suilysin.

Results: In culture medium H₂O₂ concentrations as low as 1 mM impaired bacterial growth even in the presence of Dpr, whereas higher H₂O₂ concentrations of 5 mM led to killing of the Dpr-deficient mutant but not of the wild type (wt). The addition of iron to the culture medium increased the toxic effect of H₂O₂ to the mutant but not the wt. Preliminary results showed that H₂O₂ concentrations as high as 5 mM did not kill S. suis, in porcine serum or CSF even in the absence of Dpr unless iron was added, leading to a certain level of killing of the mutant.

Summary: Our results underline the role of Dpr in protection against ROS in the presence of high iron concentrations and suggest that S. suis possess additional mechanisms to protect itself from killing by H₂O₂. During infection, S. suis-caused hemolysis might account for high iron levels in body fluids and render Dpr important for survival. Further experiments are planned to better understand its role in the pathogenesis of S. suis infection.