Open AccessAcacetin inhibits Streptococcus pneumoniae virulence by targeting pneumolysin
Author(s) -
Li Shufang,
Lv Qianghua,
Sun Xiaodi,
Tang Tianzhong,
Deng Xuming,
Yin Yunhou,
Li Li
Publication year - 2020
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.13279
Subject(s) - pneumolysin , streptococcus pneumoniae , microbiology and biotechnology , acacetin , in vivo , virulence , biology , in vitro , cytotoxicity , virulence factor , antibiotics , biochemistry , apigenin , flavonoid , gene , antioxidant
Objectives Streptococcus pneumoniae ( S. pneumoniae ) is an important commensal and pathogenic bacterium responsible for pneumonia, meningitis and other invasive diseases. Pneumolysin (PLY) is the major virulence factor that contributes significantly to the interaction between S. pneumoniae and the host. Key findings In this study, the results of antibacterial analysis, the haemolysis test and the Western blotting assay showed that acacetin inhibited PLY‐mediated pore‐forming activity caused by S. pneumoniae culture precipitates and purified PLY without anti‐ S. pneumoniae activity. In addition, acacetin treatment inhibited PLY oligomerization without affecting the expression of PLY in S. pneumoniae culture supernatants. Live/dead cells and cytotoxicity assays suggested that acacetin significantly enhanced the survival rate of injured cells by inhibiting the biological toxicity of PLY without cytotoxicity in the coculture system. The in vivo mouse model of S. pneumoniae infection further demonstrated that acacetin treatment could significantly reduce the levels of inflammatory factors (INF‐γ and IL‐β) in bronchoalveolar lavage fluid (BALF) and alleviate the pathological damage of lung injury. Conclusions Taken together, the results presented in this study indicated that acacetin inhibited the pore‐forming activity of PLY and reduced the virulence of S. pneumoniae in vivo and in vitro , which may provide a leading compound for the treatment of S. pneumoniae infection.