Acacetin inhibits Streptococcus pneumoniae virulence by targeting pneumolysin.
A549 Cells
Animals
Anti-Bacterial Agents
/ pharmacology
Bacterial Proteins
/ antagonists & inhibitors
Bronchoalveolar Lavage Fluid
/ immunology
Disease Models, Animal
Female
Flavones
/ pharmacology
Hemolysis
/ drug effects
Host-Pathogen Interactions
Humans
Inflammation Mediators
/ metabolism
Interferon-gamma
/ metabolism
Interleukin-1beta
/ metabolism
Lung
/ drug effects
Mice, Inbred BALB C
Microbial Viability
/ drug effects
Pneumonia, Pneumococcal
/ drug therapy
Streptococcus pneumoniae
/ drug effects
Streptolysins
/ antagonists & inhibitors
Virulence
Streptococcus pneumoniae
acacetin
antivirulence
pneumolysin
Journal
The Journal of pharmacy and pharmacology
ISSN: 2042-7158
Titre abrégé: J Pharm Pharmacol
Pays: England
ID NLM: 0376363
Informations de publication
Date de publication:
Aug 2020
Aug 2020
Historique:
received:
05
11
2019
accepted:
04
04
2020
pubmed:
12
5
2020
medline:
14
4
2021
entrez:
12
5
2020
Statut:
ppublish
Résumé
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. 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. 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.
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Flavones
0
IFNG protein, mouse
0
IL1B protein, mouse
0
Inflammation Mediators
0
Interleukin-1beta
0
Streptolysins
0
plY protein, Streptococcus pneumoniae
0
Interferon-gamma
82115-62-6
acacetin
KWI7J0A2CC
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1092-1100Subventions
Organisme : National Natural Science Foundation of China
ID : 81360656
Organisme : Jilin Provincial Department of Education
ID : JJKH20190173KJ
Organisme : Jilin Provincial Department of Education
ID : )
Informations de copyright
© 2020 Royal Pharmaceutical Society.
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