pdh modulate virulence through reducing stress tolerance and biofilm formation of Streptococcus suis serotype 2

Area of Science:

• Microbiology
• Pathogen Research
• Biochemistry

Background:

• Streptococcus suis serotype 2 (S. suis 2) is a zoonotic pathogen causing severe diseases in pigs and impacting public health.
• Pyruvate dehydrogenase (PDH) is a key enzyme in sugar metabolism, essential for energy production in various organisms.

Purpose of the Study:

• To investigate the role of pyruvate dehydrogenase (PDH) in the pathogenesis and virulence of S. suis 2.
• To determine the impact of PDH deletion on bacterial stress resistance, adhesion, invasion, and biofilm formation.

Main Methods:

• Construction and characterization of a pdh deletion strain (Δpdh) of S. suis 2.
• Infection studies in a mouse model to assess bacterial load and survival.
• In vitro assays evaluating bacterial adhesion, invasion, biofilm formation, and stress resistance (temperature, salt, oxidative).
• Real-time PCR to analyze gene expression, particularly adhesion-related genes.
• Macrophage survival assays.

Main Results:

• The Δpdh strain exhibited significantly reduced virulence in a mouse infection model compared to the wild-type (WT) strain.
• Bacterial distribution in blood and organs was lower in mice infected with Δpdh.
• The Δpdh strain showed decreased survival under temperature, salt, and oxidative stress.
• Adhesion to and invasion of PK15 cells, biofilm formation, and stress resistance were significantly impaired in Δpdh.
• PDH deletion led to reduced expression of multiple adhesion-related genes.
• The Δpdh strain had significantly lower survival rates in RAW264.7 macrophages compared to WT.

Conclusions:

• Pyruvate dehydrogenase (PDH) plays a significant role in the pathogenesis of S. suis 2.
• The reduced virulence of the Δpdh strain is associated with decreased stress resistance and impaired adhesion/invasion capabilities.
• Targeting PDH could be a potential strategy to control S. suis 2 infections.