Acacetin attenuates Streptococcus suis virulence by simultaneously targeting suilysin and inflammation

Area of Science:

• Microbiology and Immunology
• Infectious Diseases
• Pharmacology

Background:

• Streptococcus suis (S. suis) is a significant zoonotic pathogen causing severe infections in humans and animals.
• Drug-resistant S. suis strains necessitate novel therapeutic approaches.
• Suilysin (SLY) is a key virulence factor in S. suis capsular type 2 (SS2) infections, and controlling inflammation is crucial for mitigating damage.

Purpose of the Study:

• To identify inhibitors of S. suis virulence factor suilysin (SLY).
• To evaluate the potential of acacetin in mitigating S. suis-induced inflammation and cell injury.
• To explore acacetin as a complementary therapeutic strategy for S. suis infections.

Main Methods:

• Acacetin was tested for its inhibitory effect on SLY oligomerization.
• The impact of acacetin on bacterial growth was assessed.
• Acacetin's effect on S. suis-induced inflammation and cell damage was evaluated in a co-infection system, focusing on the MAPK signaling pathway.

Main Results:

• Acacetin effectively inhibited SLY oligomerization without impacting S. suis growth.
• Acacetin (4-16 μg/ml) reduced S. suis-induced inflammation by downregulating MAPK pathway activation.
• Acacetin treatment alleviated S. suis-mediated cell injury.

Conclusions:

• Acacetin is a potent inhibitor of SLY haemolytic activity.
• Acacetin demonstrates anti-inflammatory effects by modulating the MAPK pathway.
• Acacetin represents a promising therapeutic candidate for S. suis infections, offering a dual approach of inhibiting virulence and reducing inflammation.