Canagliflozin Inhibited the Activity of Hemolysin and Reduced the Inflammatory Response Caused by Streptococcus suis

Highly virulent Streptococcus suis (S. suis) infections can cause Streptococcal toxic shock-like syndrome (STSLS) in pigs and humans, in which an excessive inflammatory response causes severe damage. Hemolysin (SLY) is a major virulence factor of S. suis serotype 2 that produces pores in the target...

Full description

Saved in:
Bibliographic Details
Published in:International journal of molecular sciences 2023-09, Vol.24 (17), p.13074
Main Authors: Li, Xiaodan, Li, Qingyuan, Zhang, Zhaoran, Wang, Chenchen, Huo, Xinyu, Lai, Hongjiang, Lu, Hao, Lu, Wenjia, Qian, Yulin, Dong, Wenqi, Tan, Chen, Liu, Manli
Format: Article
Language:English
Subjects:
Antibiotics
Antidiabetics
Antimicrobial agents
Bacteria
Cytokines
Drug resistance
Gram-positive bacteria
Libraries
Mortality
Pathogens
Proteins
Sepsis
Staphylococcus infections
Streptococcus infections
Toxicity
Virulence
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Highly virulent Streptococcus suis (S. suis) infections can cause Streptococcal toxic shock-like syndrome (STSLS) in pigs and humans, in which an excessive inflammatory response causes severe damage. Hemolysin (SLY) is a major virulence factor of S. suis serotype 2 that produces pores in the target cell membrane, leading to cytoplasmic K+ efflux and activation of the NLRP3 inflammasome, ultimately causing STSLS. The critical aspect of hemolysin in the pathogenesis of S. suis type 2 makes it an attractive target for the development of innovative anti-virulence drugs. Here, we use the S. suis toxin protein (SLY) as a target for virtual screening. A compound called canagliflozin, a hypoglycemic agent, was identified through screening. Canagliflozin significantly inhibits the hemolytic activity of hemolysin. The results combined with molecular dynamics simulation, surface plasmon resonance, and nano differential scanning fluorimetry show that canagliflozin inhibits the hemolytic activity of SLY by binding to SLY. In addition, canagliflozin markedly reduced the release of SC19-induced inflammatory factors at the cellular level and in mice. Importantly, the combination of canagliflozin and ampicillin had a 90% success rate in mice, significantly greater than the therapeutic effect of ampicillin. The findings suggest that canagliflozin may be a promising new drug candidate for S. suis infections.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms241713074