Effective antibacterial and anti-hemolysin activity of ellipticine hydrochloride against Streptococcus suis in mouse model.

2021 
Streptococcal toxic shock-like syndrome (STSLS) caused by the epidemic strain of Streptococcus suis leads to severe inflammation and high mortality. The life and health of humans and animals are also threatened by the increasingly severe antimicrobial resistance in Streptococcus suis (S. suis). To discover novel strategies for the treatment of S. suis is an urgent need. Suilysin (SLY) is considered to be an important virulence factor in the pathogenesis of S. suis In this study, ellipticine hydrochloride (EH) was firstly reported as a compound to antagonize the hemolytic activity of SLY. In vitro, EH was found to effectively inhibit SLY-mediated hemolytic activity. Furthermore, EH and SLY had a strong affinity, thereby directly binding to SLY to interfere the hemolytic activity. Meanwhile, it was worth noting that EH was also found to have a significant antibacterial activity. In vivo, compared with traditional ampicillin, EH could not only significantly improve the survival rate of mice infected with S. suis 2 strain Sc19, but also relieve lung pathological damage. Furthermore, EH effectively decreased the levels of inflammatory cytokines (IL-6, TNF-α) and blood biochemistry (ALT, AST, CK) in Sc19-infected mice. Additionally, EH markedly reduced the bacterial load of tissues in Sc19-infected mice. In conclusion, our findings suggest that EH can be a potential compound for treating S. suis infection in view of its antibacterial and anti-hemolysin activity.ImportanceIn recent years, the inappropriate use of antibiotics unnecessarily causes the continuous emergence of resistant bacteria. The antimicrobial resistance of Streptococcus suis (S. suis) becomes also an increasingly serious problem. Targeting virulence can reduce the selective pressure of bacteria on antibiotics, thereby alleviating the development of bacterial resistance to a certain extent. Meanwhile, the excessive inflammatory response caused by S. suis infection is considered the primary cause of acute death. Here, we found that ellipticine hydrochloride (EH) exhibited effective antibacterial and anti-hemolysin activity against S. suis in vitro. In vivo, compared with ampicillin, EH had a significant protective effect on S. suis 2 strain Sc19-infected mice. Our results indicated that EH with dual antibacterial and antivirulence effects will contribute to medicating S. suis infections and alleviating the antimicrobial resistance of S. suis to a certain extent. More importantly, EH may develop into a promising drug for the treatment of acute death caused by excessive inflammation.
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