title: Shikonin alleviates the biotoxicity produced by pneumococcal pneumolysin.
abstract: OBJECTIVE
  Streptococcus pneumoniae (S. pneumoniae) is a common pathogen that can cause severe infections in humans. Pneumolysin (PLY) is an important virulence trait of S. pneumoniae and has cytotoxicity, genotoxicity and pro-inflammatory activity; it is essential for the pathogenesis of S. pneumoniae pneumonia and is an anti-virulence target of small molecule drug development. The treatment options for this microbe were limit due to the ubiquitous antibiotic resistance; therefore, new drugs and treatment strategies are needed.
  
  
  METHODS
  Shikonin was selected by drug screening based on haemolysis assays, and its mechanism of suppressing PLY toxicity was determined by oligomerization assay. Meanwhile, the in vitro cell viability assays and in vivo experiments were performed to explore the capability of shikonin to protect cells and tissue from S. pneumoniae-mediated damage.
  
  
  RESULTS
  Shikonin was found to significantly decrease PLY-induced haemolytic activity, cytotoxicity and genotoxicity via lessening the formation of oligomers; moreover, the agent can reduce the mortality of mice caused by lethal pneumonia and mitigate the injury of target organs as well.
  
  
  CONCLUSIONS
  We suggest that shikonin could be a potent candidate for a novel therapeutic or auxiliary substance in the treatment of infections encountering insufficient vaccines and antimicrobial resistance to traditional antibiotics.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China. Postal code: 130062.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China. Postal code: 130062.
authors.forename: Yonglin
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The Affiliated Hospital of Changchun University of Chinese Medicine, Changchun, Jilin 130021, China.
authors.forename: Laiying
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China. Postal code: 130062.
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China. Postal code: 130062.
authors.forename: Dongxue
authors.initials: D
authors.lastname: Shi
authors.affiliation: The Respiratory Department of the First Hospital of Jilin University, Changchun, Jilin 130021, China. Electronic address: lisa05@yeah.net.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, College of Veterinary Medicine, Jilin University, Changchun, China. Postal code: 130062. Electronic address: wjf927@jlu.edu.cn.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D005260:Female; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D009285:Naphthoquinones / Q000494:pharmacology*; D011018:Pneumonia, Pneumococcal / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000472:pathogenicity; D013301:Streptolysins / Q000037:antagonists & inhibitors*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D009285:Naphthoquinones; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C016101:shikonin
keywords: Genotoxicit; Lethal pneumonia; Pneumolysin; Shikonin; Streptococcus Pneumoniae; Virulence