Effect of emodin on Streptococcus suis by targeting β-ketoacyl-acyl carrier protein synthase Ⅱ
Jun Wang1, Yongzheng Liu1, Chongxiang Sun1
1College of Veterinary Medicine, Northeast Agricultural University, Harbin, China.
Background:
Streptococcus suis is a zoonotic pathogen that causes meningitis, septicaemia, endocarditis, arthritis, and pneumonia in human beings. With the increasing prevalence of S. suis infections and a general decline in the effectiveness of antibiotics, the development of novel drugs that have effect on S. suis is extremely urgent. Emodin, a natural anthraquinone derivative of Rheum palmatum L., Reynoutria japonica Houtt., Polygonum multiflorum Thunb. and Cassia obtusifolia L., has been reported to exert anti-S. suis effect; however, the specific mechanism of the anti-S. suis action by targeting β-ketoacyl-acyl carrier protein synthase Ⅱ (FabF) in the fatty acid synthesis pathway remains unexplored.
Purpose:
We sought to reveal the potential role of emodin to prevent S. suis infection, investigate its mechanism of anti-S. suis action, and provide further evidence of emodin as an alternative to traditional antibiotic agents.
Methods:
The in vitro anti-S. suis properties of emodin were assessed through minimum inhibitory concentration (MIC) assays, and time-kill assays. Subsequently, the mechanisms underlying emodin's mode of action at the molecular level by targeting FabF were elucidated using molecular docking, site-directed mutagenesis, bio-layer interferometry assays, and cellular thermal shift assays. Finally, metabolomics, cell membrane phospholipid content assay and biochemical parameters assays were used to detect emodin disrupting cell membrane integrity and function by affecting fatty acid biosynthesis.
Results:
In this study, we have identified that emodin inhibits S. suis by suppressing free fatty acids (FFAs) synthesis and disrupting phospholipid production by targeting FabF, a key enzyme in the fatty acid biosynthesis pathway. This interference compromises the integrity and functionality of the cell membranes of S. suis. Emodin also triggers the dissipation of the proton motive force, accelerates the tricarboxylic acid cycle, and enhances cellular respiration, ultimately leading to S. suis cell death.
Conclusion:
This study suggested that emodin inhibits the growth of S. suis via targeting FabF and the inhibition of fatty acid biosynthesis through enzyme-targeted drug design. This represents a novel strategy for developing antimicrobial agents against S. suis and addressing the challenge of antibiotic resistance.
Insights
Emodin, a natural compound, effectively inhibits Streptococcus suis by targeting the FabF enzyme, disrupting fatty acid synthesis and cell membrane integrity. This offers a novel approach against antibiotic-resistant bacterial infections.
Area of Science:
- Microbiology
- Pharmacology
- Biochemistry
Background:
- *Streptococcus suis* is a zoonotic pathogen causing severe human infections like meningitis and pneumonia.
- Rising antibiotic resistance necessitates novel therapeutic strategies against *S. suis*.
- Emodin, a natural compound, shows potential antimicrobial effects, but its mechanism against *S. suis* is unclear.
Purpose of the Study:
- To investigate emodin's role in preventing *S. suis* infections.
- To elucidate the molecular mechanism of emodin's anti-*S. suis* action.
- To evaluate emodin as a potential alternative to conventional antibiotics.
Main Methods:
- In vitro assessment of emodin's anti-*S. suis* activity using MIC and time-kill assays.
- Molecular docking, mutagenesis, and biophysical assays to determine emodin's target (FabF).
- Metabolomics and biochemical assays to analyze effects on fatty acid biosynthesis and cell membrane integrity.
Main Results:
- Emodin inhibits *S. suis* by targeting FabF, a key enzyme in fatty acid biosynthesis.
- Emodin disrupts phospholipid production, compromising cell membrane integrity and function.
- Emodin induces cell death through proton motive force dissipation and enhanced respiration.
Conclusions:
- Emodin inhibits *S. suis* growth by targeting FabF and fatty acid biosynthesis.
- This study presents a novel enzyme-targeted drug design strategy against *S. suis*.
- Emodin offers a promising alternative for combating antibiotic resistance in *S. suis* infections.
