title: β-sitosterol interacts with pneumolysin to prevent Streptococcus pneumoniae infection.
abstract: Pneumolysin is one of the major virulence factors elaborated by Streptococcus pneumoniae; this toxin is a member of the cholesterol-dependent cytolysins. Engagement of cholesterol induces the formation of a multi-subunit complex by pneumolysin that lyses host cells by forming pores on the membrane. Because pneumolysin released by bacteria which have been killed by conventional antibiotics is still active, agents capable of directly attacking the toxin are considered advantageous against antimicrobials in the treatment of S. pneumoniae infections. Here we found that the phytosterol, β-sitosterol, effectively protects against cell lysis caused by pneumolysin. This compound interacts with the toxin at Thr459 and Leu460, two sites important for being recognized by its natural ligand, cholesterol. Similar to cholesterol, β-sitosterol induces pneumolysin oligomerization. This compound also protects cells from damage by other cholesterol-dependent toxins. Finally, this compound protects mice against S. pneumoniae infection. Thus, β-sitosterol is a candidate for the development of anti-virulence agents against pathogens that rely on cholesterol-dependent toxins for successful infections.
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Institute of Biophysics, CAS, 15 Datun Road, Chaoyang District, Beijing, 100101, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Song
authors.initials: S
authors.lastname: Meng
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Niu
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Department of Food Quality and Safety, College of Veterinary Medicine, Jilin University, Changchun, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001665:Binding Sites; D002784:Cholesterol / Q000737:chemistry / Q000378:metabolism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008168:Lung / Q000166:cytology / Q000187:drug effects; D008297:Male; D008810:Mice, Inbred C57BL; D008958:Models, Molecular; D011008:Pneumococcal Infections / Q000188:drug therapy / Q000382:microbiology; D012855:Sitosterols / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000472:pathogenicity*; D013301:Streptolysins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D012855:Sitosterols; D013301:Streptolysins; C032290:plY protein, Streptococcus pneumoniae; C025473:gamma-sitosterol; D002784:Cholesterol