Streptococcus suis Deploys Multiple ATP-Dependent Proteases for Heat Stress Adaptation.

Area of Science:

• Microbiology
• Bacterial Pathogenesis
• Stress Response

Background:

• Streptococcus suis is a zoonotic pathogen causing severe human infections.
• Bacterial pathogens must adapt to host stress, such as fever, to survive.
• Proteases play a key role in degrading misfolded proteins during stress.

Purpose of the Study:

• To investigate the role of ATP-dependent proteases in Streptococcus suis stress response.
• To understand how these proteases contribute to bacterial survival and virulence.

Main Methods:

• Analysis of Streptococcus suis protease gene expression under various stress conditions (heat, oxidative, acidic, cold).
• In vitro and in vivo studies using gene deletion mutants (ftsH, clpP) to assess bacterial survival and stress tolerance.
• Identification of regulatory mechanisms controlling protease gene expression, including the role of CtsR.

Main Results:

• Streptococcus suis encodes multiple ATP-dependent proteases (FtsH, ClpAP, ClpBP, ClpCP, ClpXP).
• Expression of ftsH, clpA/B/C, and clpP genes are upregulated by heat stress.
• FtsH and ClpP are essential for S. suis survival under heat stress in vitro and in vivo.
• Deletion of ftsH or clpP reduces tolerance to heat, oxidative, and acidic stresses, and impairs survival within macrophages.
• The repressor CtsR regulates clp operons and is inactivated by heat stress.

Conclusions:

• Multiple ATP-dependent proteases form a flexible network for heat stress response in S. suis.
• This network enables fine-tuning of protein degradation/refolding to maintain homeostasis and optimize survival during infection.
• FtsH and ClpP are critical virulence factors for S. suis, particularly under heat stress conditions.