Isopropoxy Benzene Guanidine Ameliorates Streptococcus suis Infection In Vivo and In Vitro
Ning Han1,2,3, Jie Li1,2,3, Feifei Zhao1,2,3
1Guangdong Provincial Key Laboratory of Veterinary Pharmaceutics Development and Safety Evaluation, College of Veterinary Medicine, South China Agricultural University, Guangzhou 510642, China.
Abstract:
Streptococcus suis, an encapsulated zoonotic pathogen, has been reported to cause a variety of infectious diseases, such as meningitis and streptococcal-toxic-shock-like syndrome. Increasing antimicrobial resistance has triggered the need for new treatments. In the present study, we found that isopropoxy benzene guanidine (IBG) significantly attenuated the effects caused by S. suis infection, in vivo and in vitro, by killing S. suis and reducing S. suis pathogenicity. Further studies showed that IBG disrupted the integrity of S. suis cell membranes and increased the permeability of S. suis cell membranes, leading to an imbalance in proton motive force and the accumulation of intracellular ATP. Meanwhile, IBG antagonized the hemolysis activity of suilysin and decreased the expression of Sly gene. In vivo, IBG improved the viability of S. suis SS3-infected mice by reducing tissue bacterial load. In conclusion, IBG is a promising compound for the treatment of S. suis infections, given its antibacterial and anti-hemolysis activity.
Insights
Isopropoxy benzene guanidine (IBG) shows promise for treating Streptococcus suis infections. This compound effectively kills bacteria and reduces pathogenicity by disrupting cell membranes and inhibiting suilysin.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Streptococcus suis is a zoonotic pathogen causing severe infections like meningitis.
- Rising antimicrobial resistance necessitates novel therapeutic strategies.
- Existing treatments face challenges due to bacterial resistance.
Purpose of the Study:
- To evaluate the efficacy of isopropoxy benzene guanidine (IBG) against Streptococcus suis.
- To investigate the mechanisms underlying IBG's antimicrobial and anti-pathogenicity effects.
- To assess IBG's therapeutic potential in vivo and in vitro.
Main Methods:
- In vitro assays to determine IBG's effect on S. suis viability and pathogenicity.
- Analysis of IBG's impact on bacterial cell membrane integrity and proton motive force.
- In vivo studies using a mouse model of S. suis infection.
- Assessment of IBG's effect on suilysin activity and Sly gene expression.
Main Results:
- IBG demonstrated significant in vitro and in vivo attenuation of S. suis infection.
- IBG disrupted S. suis cell membrane integrity, increasing permeability.
- IBG inhibited suilysin activity and reduced Sly gene expression, improving mouse survival rates.
Conclusions:
- IBG exhibits potent antibacterial activity against S. suis.
- IBG possesses anti-hemolysis properties by targeting suilysin.
- IBG represents a promising therapeutic candidate for treating S. suis infections.
