Apigenin protects mice from pneumococcal pneumonia by inhibiting the cytolytic activity of pneumolysin.
Streptococcus pneumoniae is an important human pathogenic bacterium that can cause various life-threatening infections. Pneumolysin (PLY), the pore-forming toxin that forms large pores in the cell membrane, is a key virulence factor secreted by S. pneumoniae that penetrates the physical defenses of the host and plays an important role in the pathogenesis of pneumococcal diseases, such as pneumonia, meningitis, bacteremia and otitis media. This study showed that apigenin, one of the bioflavonoids widely found in herbs, inhibits PLY-induced hemolysis by inhibiting the oligomerization of PLY and has no anti-S. pneumoniae activity. In addition, when PLY was incubated with human alveolar epithelial (A549) cells, apigenin could effectively alleviate PLY-mediated cell injury. In vivo studies further demonstrated that apigenin could protect mice against S. pneumoniae pneumonia. These results imply that apigenin could directly interact with PLY to decrease the pathogenicity of S. pneumoniae and that novel therapeutics against S. pneumoniae PLY might provide greater effectiveness in combatting S. pneumoniae pneumonia.
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Meng
M
Song
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Li
L
Li
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Meng
M
Li
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China.
Yonghong
Y
Cha
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China. Electronic address: dengxm@jlu.edu.cn.
Xuming
X
Deng
Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University, Changchun, China. Electronic address: wjf927@jlu.edu.cn.
Jianfeng
J
Wang
D000072283:A549 Cells; D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D005260:Female; D006461:Hemolysis; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy*; D013301:Streptolysins / Q000037:antagonists & inhibitors*
D001426:Bacterial Proteins; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; D047310:Apigenin
Anti-virulence; Apigenin; Pneumolysin; Streptococcus pneumoniae