Mn uptake system affects the virulence of Streptococcus suis by mediating oxidative stress

Area of Science:

• Microbiology
• Pathogenesis
• Nutritional Immunity

Background:

• Pathogens require essential micronutrients like manganese (Mn) during infection.
• Hosts employ nutritional immunity and oxidative stress to limit pathogen access to nutrients.
• Streptococcus suis pathophysiology regarding manganese is poorly understood.

Purpose of the Study:

• To investigate the role of manganese in Streptococcus suis pathogenesis.
• To elucidate the function and regulation of the Mn uptake system (TroABCD) in S. suis.
• To assess the potential of Mn acquisition as an antimicrobial target.

Main Methods:

• Construction and characterization of Mn uptake system (TroABCD) mutants in S. suis.
• Assessment of bacterial tolerance to calprotectin and oxidative stress.
• Evaluation of bacterial survival and virulence in a mouse model.
• Transcriptional analysis of troABCD using capping rapid amplification of cDNA ends (RACE).
• Electrophoretic mobility shift assay (EMSA) to study TroR-promoter interactions.

Main Results:

• Inactivation of the TroABCD system reduced S. suis tolerance to calprotectin and oxidative stress.
• TroABCD mutant strains exhibited decreased cellular survival and attenuated virulence in vivo.
• TroR was identified as a transcriptional repressor of the troABCD operon.
• Mutations in troR led to increased transcription of troABCD and higher intracellular Mn levels.
• EMSA confirmed direct binding of TroR to the troABCD promoter region.

Conclusions:

• Manganese acquisition via the TroABCD system is essential for S. suis pathogenesis.
• The TroR repressor regulates Mn uptake in response to manganese availability.
• The S. suis Mn uptake system represents a promising target for novel antimicrobial strategies.