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Shionone-Targeted Pneumolysin to Ameliorate Acute Lung Injury Induced by Streptococcus pneumoniae In Vivo and In Vitro.
Du, Runbao; Wang, Tian; Lv, Hongfa; Zou, Yinuo; Hou, Xiaoning; Hou, Nana; Zhang, Peng; Li, Hongen; Chi, Gefu.
  • Du R; The Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010107, China.
  • Wang T; Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130062, China.
  • Lv H; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Zou Y; Department of Laboratory Animals, College of Animal Sciences, Jilin University, Changchun 130062, China.
  • Hou X; Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130062, China.
  • Hou N; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Zhang P; Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130062, China.
  • Li H; State Key Laboratory for Zoonotic Diseases, Key Laboratory for Zoonosis Research, College of Veterinary Medicine, Jilin University, Changchun 130062, China.
  • Chi G; Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun 130062, China.
Molecules ; 27(19)2022 Sep 23.
Article in English | MEDLINE | ID: covidwho-2066272
ABSTRACT
Streptococcus pneumoniae (S. pneumoniae), as a Gram-positive bacterium, can cause severe bacterial pneumonia, and result in high morbidity and mortality in infected people. Meanwhile, isolated drug-resistant S. pneumoniae is growing, which raises concerns about strategies for combatting S. pneumoniae infection. To disturb S. pneumoniae pathogenicity and its drug-resistance, developing novel anti-infective strategies or compounds is urgent. In this study, the anti-infective effect of shionone was explored. A minimum inhibitory concentration (MIC) assay and growth curve determination were performed to evaluate the effect of the tetracyclic triterpenoid compound shionone against S. pneumoniae. Hemolysis tests, western blotting, oligomerization inhibition assays, and molecular docking were carried out to explore the anti-infective mechanism of shionone. Moreover, the protective effect of shionone was also confirmed in a mousepneumonia model. The results showed that the excellent hemolytic inhibitory activity of shionone was observed at less than 8 µg/mL. Meanwhile, shionone could disturb the oligomerization of pneumolysin (PLY) but did not interfere with PLY expression at less than 4 µg/mL. Molecular docking suggested that shionone targeted the ASP-59, ILE-60, THR-57, PHE-344, and ASN-346 amino acid sites to reduce S. pneumoniae pathogenicity. Furthermore, shionone alleviated lung histopathologic injury and decreased lung bacterial colonization in vivo. The above results showed that shionone could bind to the PLY active pocket under the concentrations of 8 µg/mL and neutralize PLY hemolysis activity to reduce S. pneumoniae pathogenicity in vitro and in vivo.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Triterpenes / Acute Lung Injury Type of study: Experimental Studies Limits: Humans Language: English Journal subject: Biology Year: 2022 Document Type: Article Affiliation country: Molecules27196258

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Triterpenes / Acute Lung Injury Type of study: Experimental Studies Limits: Humans Language: English Journal subject: Biology Year: 2022 Document Type: Article Affiliation country: Molecules27196258