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Intracranial Subarachnoidal Route of Infection for Investigating Roles of Streptococcus suis Biofilms in Meningitis in a Mouse Infection Model
Published on: July 1, 2018
Methyl anthranilate deteriorates biofilm structure of Streptococcus suis and antagonizes the capsular polysaccharide
Shuji Gao1, Yamin Shen1, Shuo Yuan1
1College of Animal Science and Technology, Henan University of Science and Technology, Luoyang, China; Henan Provincial Engineering Research Centre for Detection and Prevention and Control of Emerging Infectious Diseases in Livestock and Poultry, Luoyang, China.
Background:
Streptococcus suis is an important zoonotic pathogen that often causes biofilm-associated infection. Bacterial biofilm-dependent infection is associated with enhanced drug resistance, making it difficult to eradicate. Novel therapeutic approaches are required urgently to treat infections associated with S. suis biofilm. This study aimed to investigate the effects and mechanisms of methyl anthranilate (MA) on S. suis biofilm.
Methods:
The effect of MA on S. suis biofilm was determined using the crystal violet method, and the microstructure of the biofilm was observed by electron microscopy. The effects on capsular polysaccharides were determined using the phenol-sulphuric acid method and high-performance liquid chromatography. Adhesion and antiphagocytosis properties of S. suis were detected via cell assays. Molecular docking, molecular dynamics simulation and enzyme activity inhibition assays were used to further explore the effect of MA on AI-2 quorum sensing (QS) of S. suis. Finally, the therapeutic effect of MA was investigated using a mouse infection model.
Results:
MA destroyed the structure of S. suis biofilm, hindered biofilm formation, and reduced the synthesis of capsular polysaccharides significantly, which further weakened the adhesion and antiphagocytosis ability of S. suis. MA had a docking effect and binding site (SER76 and ASP197) similar to S-adenosylhomocysteine (SAH). Further analysis showed that MA competitively bound 5'-methyladenosine/S-adenosine homocysteine nucleosidase with SAH to interfere with AI-2 QS. In a mouse model, MA reduced the bacterial burden and inflammatory infiltrates effectively.
Conclusion:
This study revealed the antibiofilm effects of MA, and highlighted its potential as a QS inhibitor against S. suis infection.
Insights
Methyl anthranilate (MA) disrupts Streptococcus suis biofilms by inhibiting capsular polysaccharide synthesis and quorum sensing. This compound shows potential as a novel therapeutic agent against S. suis infections.
Area of Science:
- Microbiology
- Infectious Diseases
- Drug Discovery
Background:
- *Streptococcus suis* is a significant zoonotic pathogen
- Biofilm formation in *S. suis* infections leads to increased drug resistance
- Novel treatments are needed for *S. suis* biofilm infections
Purpose of the Study:
- To investigate the effects of methyl anthranilate (MA) on *S. suis* biofilms
- To elucidate the mechanisms underlying MA's action against *S. suis*
- To evaluate MA as a potential therapeutic agent
Main Methods:
- Crystal violet assay and electron microscopy for biofilm structure analysis
- Phenol-sulphuric acid method and HPLC for capsular polysaccharide quantification
- Cell assays for adhesion and antiphagocytosis
- Molecular docking, simulations, and enzyme inhibition assays for quorum sensing (QS) analysis
- Mouse infection model for therapeutic evaluation
Main Results:
- MA significantly disrupted existing biofilms and inhibited new biofilm formation
- MA reduced capsular polysaccharide synthesis, weakening bacterial adhesion and antiphagocytosis
- MA competitively inhibited AI-2 QS by binding to 5'-methyladenosine/S-adenosine homocysteine nucleosidase
- MA treatment effectively reduced bacterial load and inflammation in a mouse model
Conclusions:
- Methyl anthranilate exhibits potent antibiofilm properties against *Streptococcus suis*
- MA acts as a quorum sensing inhibitor, offering a novel therapeutic strategy
- MA demonstrates significant potential for treating *S. suis* infections
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