Canagliflozin Inhibited the Activity of Hemolysin and Reduced the Inflammatory Response Caused by <i>Streptococcus suis</i>

Canagliflozin Inhibited the Activity of Hemolysin and Reduced the Inflammatory Response Caused by <i>Streptococcus suis</i>

Highly virulent <i>Streptococcus suis</i> (<i>S. suis</i>) 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 <i>S. sui...

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Bibliographic Details
Main Authors: Xiaodan Li, Qingyuan Li, Zhaoran Zhang, Chenchen Wang, Xinyu Huo, Hongjiang Lai, Hao Lu, Wenjia Lu, Yulin Qian, Wenqi Dong, Chen Tan, Manli Liu
Format: Article
Language:English
Published: MDPI AG 2023-08-01
Series:International Journal of Molecular Sciences
Subjects:
<i>Streptococcus suis</i>
hemolysin
canagliflozin
anti-hemolysin
Online Access:https://www.mdpi.com/1422-0067/24/17/13074
Description
Summary:Highly virulent <i>Streptococcus suis</i> (<i>S. suis</i>) 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 <i>S. suis</i> serotype 2 that produces pores in the target cell membrane, leading to cytoplasmic K<sup>+</sup> efflux and activation of the NLRP3 inflammasome, ultimately causing STSLS. The critical aspect of hemolysin in the pathogenesis of <i>S. suis</i> type 2 makes it an attractive target for the development of innovative anti-virulence drugs. Here, we use the <i>S. suis</i> 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 <i>S. suis</i> infections.
ISSN:1661-6596
1422-0067

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