title: Morin AttenuatesStreptococcus suisPathogenicity in Mice by Neutralizing Suilysin Activity.
abstract: Streptococcus suis, a Gram-positive pathogen, is widely recognized as an important agent of swine infection, and it is also known to cause a variety of zoonoses, such as meningitis, polyarthritis and pneumonia. Suilysin (SLY), an extracellular pore-forming toxin that belongs to the cholesterol-dependent cytolysin family, is an essential virulence factor ofS. suiscapsular type 2 (SS2). Here, we found that morin hydrate (morin), a natural flavonoid that lacks anti-SS2 activity, inhibits the hemolytic activity of SLY, protects J774 cells from SS2-induced injury and protects mice from SS2 infection. Further, by molecular modeling and mutational analysis, we found that morin binds to the "stem" domain 2 in SLY and hinders its transformation from the monomer form to the oligomer form, which causes the loss of SLY activity. Our study demonstrates that morin hinders the cell lysis activity of SLY through a novel mechanism of interrupting the heptamer formation. These findings may lead to the development of promising therapeutic candidates for the treatment of SS2 infections.
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Gen
authors.initials: G
authors.lastname: Li
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Gejin
authors.initials: G
authors.lastname: Lu
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Qi
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University Changchun, China.
authors.forename: Hongen
authors.initials: H
authors.lastname: Li
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin University Changchun, China.
authors.forename: Yanhui
authors.initials: Y
authors.lastname: Wang
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Bowen
authors.initials: B
authors.lastname: Liu
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Xiaodi
authors.initials: X
authors.lastname: Niu
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Xuming
authors.initials: X
authors.lastname: Deng
authors.affiliation: The First Hospital and Institute of Infection and Immunity, Jilin UniversityChangchun, China; Key Laboratory of Zoonosis, Ministry of Education, Institute of Zoonosis, College of Veterinary Medicine, Jilin UniversityChangchun, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
keywords: Streptococcus suis; anti-infective; molecular modeling; morin; suilysin